Health Longevity Secrets

Keto = Death? with Dr Dom D'Agostino

• Robert Lufkin MD • Episode 223

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Ready to revolutionize your understanding of metabolism? Dr. Dominic D'Agostino takes us deep into the science of ketosis, revealing why this evolutionary metabolic state might be the missing link in our modern health crisis.

The keto revolution isn't just about weight loss. As Dr. Dom explains, ketosis fundamentally changes our physiology in ways that impact every major system in our body. While our ancestors regularly shifted in and out of this fat-burning state, most modern humans never experience it—silencing what might be a powerful tool for combating today's chronic disease epidemic.

What makes ketosis unique? Unlike other dietary approaches, a properly implemented ketogenic diet actually changes brain neurochemistry, reduces inflammation, and improves metabolic markers across the board. That's why it's proven effective for conditions ranging from epilepsy to diabetes, hypertension to neurodegenerative diseases. It's not a "magic bullet" but rather a "magic shotgun" addressing multiple pathways simultaneously.

Perhaps most compelling is the research showing ketosis can improve metabolic flexibility, enhance cognitive function, and potentially contribute to longevity through mechanisms like reduced inflammation and improved mitochondrial health. In a world where 72% of Americans struggle with weight issues and chronic diseases continue rising, could this metabolic switch be a key to reversing these trends?

Discover why research into ketogenic therapies has exploded in recent years, with hundreds of clinical trials underway exploring applications from metabolic disorders to cancer adjunctive care. 

ketonutrition.org

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Speaker 1:

Welcome back to the event. Our guest today will be speaking on ketosis and how it creates longevity and health. You're going to learn specifically what ketosis is and how to stay in ketosis and all the benefits of it when you stay to the end. Our presenter for this discussion is Dr Dominic D'Agostino PhD. He's a tenured associate professor at the University of South Florida College of Medicine in the Department of Molecular Pharmacology and Physiology. He teaches medical neuroscience, medical physiology, nutrition and neuropharmacology. His primary research focuses on developing and testing nutritional and metabolic-based therapies for a variety of disease states. So he really knows what he's talking about. So let's go ahead and jump on in. Here we go, hey, dom, welcome.

Speaker 2:

Thank you, Rob. It's great to be on. I appreciate it.

Speaker 1:

I'm so excited to talk about a subject near and dear to my heart ketosis and ketogenic diets but before we dive into it, maybe just start. What exactly do we mean when people say ketosis? What exactly is that?

Speaker 2:

do we mean when people say ketosis? What exactly is that? Yeah, ketosis is defined by an objective biomarker that we can measure in our urine, in our blood or even in our breath, and that's the ketone bodies beta-hydroxybutyrate, acetoacetate or acetone. So you can achieve ketosis through fasting, you could achieve it through manipulating macronutrient ratios, and that's called the ketogenic diet. And you can also achieve it, more recently, with exogenous ketones, ketone esters, ketone salts or even medium chain triglycerides, which is a type of ketogenic fat type of ketogenic fat.

Speaker 1:

Now are most people in ketosis, or what is the? What is the? What's the alternative to ketosis?

Speaker 2:

I guess the alternative to ketosis would be not in ketosis. So the standard American diet, and pretty much what we're told to eat, silences or suppresses a metabolic state that has enormous favorable effects on our physiology. So if we adhere to the standard American diet, one really never achieves ketosis. That means an elevation of blood ketones 0.5 millimolar, and this is in contrary to how we evolved evolutionarily. Through limited food availability and limited carbohydrate availability, we were undoubtedly going in and out of ketosis all the time. So it's rather unnatural not to ever achieve a state of ketosis which the large majority of the population never really enters. A state of ketosis which the large majority of the population never really enters, a state of ketosis.

Speaker 1:

So historically, prior to the agricultural revolution at least, our natural state is in and out of this ketosis. But today, through the diet, largely people are no longer in it and this has effects on our health. Presumably. What's good about ketosis or what's bad about not being in ketosis ever?

Speaker 2:

Well, the ketogenic diet mimics the state of ketosis through a dietary manipulation that involves eating a sufficient amount of calories that are eucaloric means that you're not gaining weight or losing weight and what that does. In the 1920s it was developed for epilepsy and other seizure disorders. So the clinical use of the ketogenic diet starts there. Maybe you could go back to like the Banting diet. Actually, it was used for type one diabetes prior to the advent of insulin therapy, to help keep type one diabetics alive.

Speaker 2:

Essentially and I think we've known you know well if we want to take a big step back in millennia since the time of Hippocrates Well, if we want to take a big step back in millennia since the time of Hippocrates, and even you know the gospel of Mark like talks about fasting for seizures.

Speaker 2:

So we've we've known about the benefits of of ketosis achieved through fasting. And then in the 1920s the ketogenic diet was developed that is restricted in carbohydrates, very high in fat and adequate in protein. And then this diet mimics the state of fasting, or some aspects of fasting, and it not only changes our metabolic physiology, it changes our brain, neurochemistry and neuropharmacology in a way that can have a neuroprotective effect and have an anti-seizure effect and that's kind of like what we study in the lab. You know, trying to understand fundamentally. You know how changing our metabolic physiology changes other aspects of our brain health, including neurotransmitter systems. You know antioxidant status, inflammation, things like that. And I think over the last 15 years there has been an explosion of emerging applications of therapeutic ketosis. So that's a big thrust of what we do.

Speaker 1:

Yeah, I mean it's amazing what this ketogenic therapy can do for, like you say, for seizure patients or, in the past, for type one diabetics. But you know most of us don't have seizures or type one diabetes, so what are the benefits to like everyday people? You talked about brain health and what are some of the things. What are some of the benefits of being in ketosis through either a ketogenic diet or fasting, or exogenous ketones, as you mentioned?

Speaker 2:

Yeah, there are many. We tend to study, we research things that have a fundamental mechanism associated with that particular pathology that therapeutic ketosis can treat. But if we talk about the general population is what you're asking, I think I think I saw statistics yesterday. I was reading a systematic meta analysis review. It was something like 72.7% of the population is overweight and are like have, like you know, essentially. So they're like, right on, they're either obese or they fit in that category that they're overweight or obese. So that's a significant and it increases as the age increases.

Speaker 2:

So one could say that, uh, that low carb diets, uh, which are kind of create a mild state of ketosis, or ketogenic diets by virtue of increasing our body's metabolic flexibility and our ability to burn fat as fuel and suppress the hormone insulin. So that you know, 72% of people who are, you know, overweight and obese undoubtedly have although it's not part of a comprehensive metabolic panel have hyperinsulinemia, which actually occurs prior to getting type 2 diabetes. So if we were to measure hormones throughout, you know, longitudinally, throughout the trajectory of someone's metabolic health as they age, by the time that you have type 2 diabetes, that could have been predicted years before as an increasing level of insulin, the insulin level. Your pancreas is secreting more and more insulin to basically dispose of the glucose over time. So I know it's like a long-winded version to answer your question, but I think there are.

Speaker 2:

We have a situation where, at least in the US and even abroad, where we have type two diabetes, obesity, people are overweight and nutritional ketosis and even just a low carb carbohydrate restricted diet or intermittent fasting or time restricted feeding are all ways to to improve insulin sensitivity but also to create a caloric deficit, which in and of itself basically restores our health. You know our insulin sensitivity. We tend to lose weight. You can lose weight through many different ways, but we're of the opinion that if you improve insulin sensitivity lower blood glucose, lower insulin that's going to fundamentally change the neural circuitry and reward mechanisms in the brain to allow someone to comfortably lose weight over time, instead of having blood glucose fluctuations and cravings associated with eating carbohydrates, which can be a trigger for many people not all people, but for the majority of people trigger for many people, not not all people, but for the majority of people.

Speaker 1:

Yeah, I mean it's. It's so fascinating for, like, from a medical perspective, look at, look at, like you say, obesity. Most, most adult Americans are either overweight or obese and and a ketogenic diet will, will cause people to lose weight. Half of adult Americans have hypertension. A ketogenic diet, will you know, even a low-carb diet will lower blood pressure and reverse hypertension in many patients.

Speaker 2:

That's a big one, yep.

Speaker 1:

The number one killers for us all are cardiovascular disease, heart attack and stroke. A ketogenic diet will mitigate against endovascular disease and atherosclerosis.

Speaker 1:

Cancer is a big killer Ketogenic diet is now being used as secondary treatments, as we can talk about, for cancer, Alzheimer's disease. Ketogenic diet in a significant number of patients not all but reverses the effects of Alzheimer's disease and then psychiatric disease. What is it about a ketogenic diet that applies to every disease that I can think of, that is, every significant chronic disease that's epidemic in the population today. What's the underlying? What's going on?

Speaker 2:

there. Yeah, okay. So all these things that you mentioned are true. Just go to. Well, if you go to PubMed, a lot of people ask you know they're like well, what happened to the ketogenic diet? I heard about it but I don't hear much about it anymore. It's not that popular. Well, I evaluate the uh, the interest in ketogenic diet based on peer reviewed research on PubMed. So just go to PubMed. And there were something like 503 articles in 2002. And this year it's like 626 or something. So it's exponentially increasing. So the peer reviewed publications on on PubMed you just type in ketogenic diet is increasing and I think more.

Speaker 2:

What I'm more excited about is if you go to clinicaltrialsgov and type in the word ketogenic diet, you will find hundreds of research, registered clinical trials on the ketogenic diet. Now, about a third of them, if you look deep, they're also using some kind of ketone supplementation that could be MCT or ketone ester or something like that. And it's an interesting avenue of, you know, innovation in the diet. But the the general nutrition person who basically, if you ask that question, they would say well, the only, there's nothing magical about the ketogenic diet, it does nothing special at all. The only reason that it works for these things type two diabetes, weight loss and even other neuro a lot of. The only reason that it works, they'll tell you, is because a ketogenic diet is hypo palatable, the taste bad, so people eat less. And uh, and I think some may argue you know, it's hyper, it is satiating, it's, you know, fat and protein is satiating relative to carbohydrate feedings. So that's what they would say.

Speaker 2:

But I would say, I would argue that the ketogenic diet is unique and unlike any other diet, because no other diet can you follow that can control drug resistant epilepsy, like a vegan diet doesn't do it, you know. A paleo diet doesn't do it. A vegetarian, you know, the only diet that can fundamentally change our metabolic physiology, to change our brain, neurocircuitry and neuropharmacology, is a ketogenic diet. And that's why so many, you know, pharmaceutical companies are interested in the mechanism of this. I've spoken at many pharmaceutical companies. They they want me to give like one answer.

Speaker 2:

But the thing is, the ketogenic diet it's not a magic bullet, it's like a magic shotgun. So it's changing brain energy. It's changing the glutamate to GABA ratio. It's changing inflammatory mechanisms. It's changing the glutamate to GABA ratio. It's changing inflammatory mechanisms. It's changing our lab studies, the epigenetic effects of ketones. So we look at something called beta-hydroxybutyrolation, where beta-hydroxybutyrate can directly interact with histone and cause histone modifications. That's really going down the rabbit hole, but it just gives you a little bit of a sense of the pleiotropic effects associated with being in a state of ketosis.

Speaker 1:

Yeah, I mean, my personal favorite mechanism is mTOR and turning down mTOR. Turning off or turning down mTOR to autophagy, turning down inflammation, turning down hyperfunction and thus not only the chronic diseases but slowing down aging, you know, as an effect as well, and improving longevity. Now, when we talked about a ketogenic diet before we talked about it for you mentioned, for epilepsy or some of these like as treatments and that sort of thing Are any people going on ketogenic diets and just switching to ketogenic diets, or is it like, oh, I have epilepsy, I'll do it for a week and then I'll stop? I mean, is it realistic to be on a ketogenic diet for the rest of your life and not make it a diet but just a lifestyle?

Speaker 2:

Yeah, yeah, good question. I probably should have started off with this.

Speaker 2:

A ketogenic diet is a clinical intervention, that is, should involve it should require close medical supervision by, for example, in epilepsy, you have a neurologist that's working with a registered dietician that's trained in ketogenic therapies to manipulate the macronutrient ratios and to measure the person's blood or urine ketones to induce and sustain therapeutic ketosis to metabolically manage that particular disorder. So that is unlike any diet that I know of, so it's unique in that way and also an objective biomarker to help guide the clinician and the patient to manage it. However, you know you can you can use versions of the key. Our keynote speaker at the Metabolic Health Summit that just happened a few weeks ago was Dr Walter Longo. He is an advocate of the fasting mimicking diet, which is a type of a ketogenic diet. In his presentation he basically showed that it produces a state of ketosis but it's only like five days out of a month, and that what's very interesting about this intermittent ketosis is that you get sustained effects, metabolic effects that occur for weeks. Uh, I think he should like three weeks after, like a fasting mimicking diet and just like a short phase like five. Five days could be achieved. So for the everyday person and I mean he's using it to treat different disorders and stuff too but I think there's a lesson to learn here that intermittently entering a state of ketosis can produce long lasting beneficial effects on many different uh on our physiology, and this could be inflammation, this could be insulin sensitivity, it could be body weight um blood glucose control.

Speaker 2:

So I think that's an important message too, that there are many types of ketogenic diets. Uh, macronutrient ratios wise. There's a modified Atkins diet that's used for adult epilepsy. Uh, there's the fasting mimicking diet there. Wise, there's a modified Atkins diet that's used for adult epilepsy. There's the fasting mimicking diet, there's there's. Even, you know, the very first article I ever wrote in the keto nutrition blog, which is our website. Keto nutrition was a plant based ketogenic diet. Just because I get so many questions about people that are vegan or vegetarian that want to follow a ketogenic diet, so it sent me down the rabbit hole is like, okay, this is an important topic, so you can even, you know, follow a, a plant based version of a ketogenic diet if you want to.

Speaker 1:

Yeah, it's fascinating. Walter's a friend of mine and he's he's on this program, but I, you know he, as you mentioned, they have this five day fasting mimicking diet and you know he's just great. You got to try it and I go. Hey, walter, I I'm in ketosis almost all the time. I eat one meal a day and the meal I eat is, you know, basically protein and fat, very, very little refined carbs at least. So I'm in ketosis. Why would I want to do a fasting mimicking diet? And he goes. Well, he was pointed out something I hadn't thought of. Well, the ketosis is very different than fasting.

Speaker 1:

I mean there are a lot of similarities and there are a lot of overlap. But he says you're going to be in ketosis all the time but you're not, you're not fasting, and his whole fasting mimicking diet. It's basically it's like a ketogenic diet, but hypocaloric to the point of you know, 500 calories, 800 calories a day. So it drops you into this non sustainable, you know, sort of artificial stress, hypocaloric state for at least five days. And I mean nobody really knows, certainly I don't know, you know, but there there appear to be benefits from from it that above and beyond what I would get from my, you know, my daily 20 hour fast or something which really only you know only kicks in some of the, some of the autophagy for short periods, if at all, really. But yeah, it's. There's so many, so many fascinating things to look at this.

Speaker 1:

But what's the pushback on a ketogenic diet? I mean you hear negative things about it. Oh, don't do that, you'll kill your kidneys or you're you know you'll what? What do you think? What's the message people need to understand about the dangers of the ketogenic diet? Are, you know what do we need to watch out for, if there are any, versus what's out there in the press if there are any versus what's out there in the press.

Speaker 2:

Yeah Well, like any really strict medical or dietary intervention, it can have some side effects. The side effects of ketogenic diets are typically transient and manageable From the epilepsy world. If you have a fatty acid oxidation disorder, if you have pancreatitis, if you have liver dysfunction, if you have carnitine deficiency, primary carnitine deficiency if you follow a ketogenic diet, a lot of labs I've seen actually show you end up having being low in carnitine, especially if you don't have a lot of meat in the diet. That's because carnitine transports fat into the mitochondria and it tends to deplete because you're burning so much fat. So these are some of what show up in the lab. Also, low calcium and low magnesium and electrolytes especially. That can contribute to the brain fog or the keto flu in the beginning. Suppressing the hormone insulin has a natriuretic effect and also a diuretic effect, so you'll excrete more sodium and then you'll. If you're not hydrating and getting an extra electrolytes, then you're going to be hypovolemic and you could have things like orthostatic hypotension If you stand up. That's quite common, especially if you're on blood pressure medication. Probably and there's good literature to support Dietary therapies can help lower blood pressure. But low carb, ketogenic diets lower blood pressure more than any other type of diet. That's important because you could have side effects. If you are on blood pressure lowering medication, so you need to adjust the medication. That's going, because you could have side effects. If you are on blood pressure lowering medication, so you need to adjust the medication. That's going to be important.

Speaker 2:

But in regards to like pushback, I think the biggest pushback comes from cardiologists and from advocates of plant-based diets or lower fat diets, in that the fat could be atherogenic, especially if it's saturated fat. The elevation of LDL and ApoB, even in the context of improving other biomarkers like triglycerides, hemoglobin A1C, insulin levels go down. I would say in about maybe a third of the people who follow a strict ketogenic diet and lose weight and sustain it. They may have an well. If you start off with your LDL very high and you go on a ketogenic diet, it tends to come down. However, if you're healthy and lean and follow a ketogenic diet and become fat adapted, what we typically see in some people could fit what's called the lean mass hyper responder phenotype, where you have low triglycerides under 60, high HDL over 60. But then your LDL is like above 190 or above 200. So I actually fit into that category. So this is many.

Speaker 2:

The large majority of the medical establishment and especially cardiologists, are going to have a knee jerk reaction and say this diet is going to kill you. You know, get off this diet and alter the diet. But a lot of people follow ketogenic diet, gets so many great benefits from it they don't want to get off of it. So you have two options you can lower the saturated fat and see what that does and just include monounsaturated, polyunsaturated fat. Or you could take a lipid lowering medication that could be edzetamide, that could be PCSK9 inhibitor or statin. The last one, I think, has too many side effects to consider unless you have a high atherogenic risk or unless you've had a heart attack, unless you have high heart disease in the family. So that's probably the biggest pushback and a lot of people just some people just can't tolerate the level of fat needed to be on a ketogenic diet. So, like I have done over the years, as I've gravitated more towards a low carb Mediterranean diet, a type of diet that puts me in a very mild state of ketosis, but then I'll put like MCT oil, mct powder oil, and I'll use a ketone electrolyte product, maybe once or twice a day, and I'm always running about one to 1.5 millimolar ketones and I think a lot of the benefits you get from being in ketosis you could achieve that.

Speaker 2:

Or, alternatively, certain days I'll do intermittent fasting. But intermittent fasting caused me to lose lean body mass over time and strength, because it was hard for me to get the amount of calories that I needed If I did intermittent fasting every day. So it becomes like I pulled the trigger on intermittent fasting. If I need to be my best and I need to, like you know, if I have a big talk coming up or I need to have, if I'm writing a grant or a paper, I'll not eat breakfast in the morning and then I'll do that maybe like twice a week, and I have to admit they're the two days that I feel the best. So I'd like to do it all the time. But at the same time, if I intermittent fast and I just have a meal at the end of the day, I tend to overeat and I just get the munchies at night. So I did intermittent fasting for many years and I still use it.

Speaker 2:

I think it's an amazing tool, but I don't want to lose any more weight now, especially as I'm, you know, approaching 50 years old and and I look at my DEXA scans over the years, I could see, you know, since I was, I don't know 10 years ago, I lost 18 pounds of lean body maps and I'm still training. I don't train like I did before, but that's a little bit alarming and I want to like stabilize and slow things down, but that's a little bit alarming and I want to like stabilize and slow things down. So I think, intermittent fasting, it was really hard for me to maintain a certain level of, like, muscle and strength Not that I'm trying to, you know, you know, be really big like a bodybuilder or a powerlifter or something like that but I do feel it's important, as we age, to prioritize that lean body mass and strength as we age feel it's important as we age to prioritize that lean body mass and strength as we age.

Speaker 1:

Yeah, absolutely. Just one point I love my vegan audience and I love my carnivore audience and, just to be clear, you can be on a ketogenic diet with plant-based fats as well as animal-based fats. It's maybe more challenging on a plant-based, but you could find them if you're willing to do it. Absolutely. Now, one of the great things about social media is you reach out and you meet all these different people.

Speaker 1:

I have a friend I met who's an Inuit in Alaska and his grandmother he has pictures of it. She literally they lived in an igloo and they were very far north and he has all these pictures of it. She literally they lived in an igloo and they were very far North and he has all these pictures of them. And they and he said they were in ice for like nine months of the year and they're basically were on a carnivore diet most of the time and even the rest of the year. It was before, you know, civilization really came to them, so they were in a carnivore diet most of the time. Are people on a carnivore diet? I mean excluding honey, and you know, if you tell me. Those sweet things are people on a carnivore diet in ketosis.

Speaker 2:

Yeah, there's a couple of groups that advocate for a pure animal-based carnivore diet, for a ketogenic carnivore diet. So paleo medicina comes to mind. They're in Budapest, hungary. I actually visited their clinic and they pulled out a lot of records, including people with cancer, with type one diabetes, type two diabetes, and showed me a lot, and they published a number of publications too. So I think that is I mean animal based ketogenic diet will give you all the micronutrients that you need. You're not going to be I mean even vitamin C. You get from meat and there are. You're not going to be deficient in anything and the blood work looks pretty good.

Speaker 2:

On the other hand, I am of the opinion of I follow more of an omnivore based ketogenic diet, although I will say the last three or four days I completely ran out of vegetables. I just didn't have time to shop, so I was eating steak, eggs, pork, fish, with no vegetables. I actually had a little bit of blueberries at nighttime, but basically almost pure carnivore aside for like a quarter, a couple of blueberries, and I felt great, you know, but I feel I feel better if I and my go-to vegetable would be broccoli florets, you know, and I cut it up also give it to my dogs, but they're. Basically it probably makes up 5% of the calories. For me it makes up carbs. May make up five, maybe 10% of the calories, but probably five.

Speaker 2:

Just because I pick high fiber carbohydrates, I pick wild blueberries, broccoli, a little bit of pistachios, maybe macadamia nuts, maybe some walnuts here and there and salads here and there, but basically it's like eggs, eggs, steak and a lot of fish. Over the last couple years I've gravitated a lot of beef, uh, but also I eat mackerel, sardines and tuna. Fish and salmon too are probably makes up almost half of my protein, uh, from from fish sources, and then shrimp and then oysters and clams and you know things like that as well, but not as much.

Speaker 1:

Sounds like a very doable diet. I mean a very doable lifestyle. If this diet this maybe not a full on ketogenic diet, but maybe a low carb diet that keeps us in ketosis a large amount of time who would benefit from? If it affects all these chronic diseases and the risk of chronic disease and longevity itself? Who do you think should be on this type of diet? If in a perfect world, what would you like to see?

Speaker 2:

Anyone that really wants to improve their metabolic health and metabolic health is a very broad term but in the research that we do, we think it's very important to measure certain metabolic biomarkers. You mentioned blood pressure and I think we don't talk about blood pressure enough. I think blood pressure really is kind of like a silent killer and actually, like I said, ketogenic diets are more effective for lowering blood pressure than any other diets, probably because of the diuretic effect, and you know diuretics are used like hydrochlorothiazide and lipid you know, to the lower blood pressure.

Speaker 2:

But I think on a ketogenic diet. But anyone looking to improve metabolic health defined as lowering, fasting blood glucose, hemoglobin A1C, fasting, insulin levels, increasing HDL decreasing, I think you could. For people who have high LDL and high ApoB, it will come down with a well-formulated ketogenic diet. So that's something to something to track. And uric acid is also something like important to measure. And I do think a lot of people say you can't build muscle or gain strength on a ketogenic diet. But if you adjust protein to 1.5 to like 1.8 grams per kilogram, now that sounds a lot, especially if you talk to Walter Longo. It sounds like quite a lot. But I think as we age, our protein requirement is higher and if we're super active, uh, it could. We could probably get away with one gram per kilogram If you're not active. If you're get away with one gram per kilogram if you're not active, if you're more sedentary and you're not looking to like build muscle.

Speaker 2:

But these things will help the everyday person. Simple, it doesn't have to be ketogenic but carbohydrate restriction, which inadvertently will produce a state of ketosis, especially if you couple some form of carbohydrate restriction with intermittent fasting or time restricted feeding. So that could be. A lot of times it's hard for people to change what they eat. It's like, it's like you, like my parents, like I can't change what they eat. But if I tell them to like hey, have your first meal at 12 noon, or something like that, and it's to eat their food within an eight hour window, then that becomes much more doable than actually changing their shopping list, you know you're an expert on exogenous ketones and then, among many other things, but exogenous ketones are, like you mentioned, mct oils things we can take that will put us in ketosis.

Speaker 1:

Now, as a person, maybe there's like your parents, maybe, or somebody who doesn't want to fool around with a diet or worry about what they eat Is that a solution to being in ketosis? Just take a lot of exogenous ketones and will that work? Or what are the trade offs there with that?

Speaker 2:

Well, I think I see them as like a supplement. You know they're not necessary, but I think they do have, um, they do have benefits that you can actually objectively measure if you're measuring objective biomarkers, right, so um, or if you're just subjectively, how you feel, your sense of energy and stuff too. So, taking an exogenous ketone supplement, for example, and getting your ketones into that one millimolar range, I wouldn't want to go higher than that. We do a lot of research with ketone esters and I think they have great medical applications, military applications, but when you spike your ketones acutely to millimolar or higher, that actually triggers a counter regulatory effect where it actually increases the release of insulin. Because that's how we actually, that's how we like.

Speaker 2:

We have a very nuanced way of keeping ketones normal in our body. As ketone levels rise, that stimulates the pancreas to release a little bit of insulin and then that turns down beta oxidation of fats in the liver and that decreases ketogenesis. Drinking a large dose of ketone ester kind of throws a monkey wrench into that, because that could suppress your own natural ketogenesis and we do see this happens. It happens with some of the agents that we study in our lab, like the ketone esters, which are more powerful. However, it doesn't happen with the ketone electrolyte salts and probably because the mineral load from the salt the sodium, potassium, magnesium and calcium that delays gastric absorption. So the rate of rise of ketones is typically the trigger for the insulin release. So you could get up to one to even two millimolar and not have any effect on insulin and still be. It doesn't disrupt your own endogenous ketone production.

Speaker 2:

So I would gravitate away from one three butane dial, away from BHB monoester, and go towards an electrolyte ketone salt preparation. That would be safe and also to combine that with MCT and that way the MCT is stimulating your own ketone production and you could theoretically achieve therapeutic ketosis with even a high-carb diet. But I'm of the opinion is like a low carb Mediterranean diet, probably a safe diet for most people to follow. We don't need two, 300 grams of carbs a day, so there's no reason. Even my highest carb day maybe like a hundred grams and a third of the carbs would be fiber, so it has very minimal glycemic response.

Speaker 2:

But for the everyday person they could get the benefits of ketones simply by incorporating MCT or just, you know, a ketone supplement might be a dollar or $2 a day or something like that. I mean, these are not expensive things. The ketone esters are more expensive and more potent, but I don't think they're necessary, so you could. And the ketone beta-hydroxybutyrate has anti-inflammatory effects. Changes GABA levels in the brain to reduce anxiety. Gaba to glutamate ratio. Has epigenetic effects. Has blood glucose lowering effects that we're just starting to understand now. It has a lot of really interesting beneficial effects that we see.

Speaker 1:

Yeah well, this has been so great, we're almost out of time. I just want to ask a couple more questions. That insulin spike you mentioned that's that's just with the non physiologic exogenous ketones really, or is that something we have to worry about when we're in on a ketogenic diet or a low carb diet?

Speaker 2:

Yeah, no, like a ketone ester. So what we've shown is that in animal models and in humans, if you ingest, for example, like 30 grams of a ketone ester, you can quickly spike your blood blood ketone levels up to three or four, five millimolar. That could be beneficial in the context of, like an intense exercise or like if you're an elite athlete or a military diver going into you know dive operations. However, so if I was to do that in a fasted state, if I take a ketone ester and I consume it, what happens is my ketone levels will shoot up to five millimolar in about 30 minutes and then after about two hours the body will metabolize and excrete some of the ketones and after about two or three hours you will be hypoketotic and also hypoglycemic because the rapid rise in ketones will release insulin and then, for reasons we don't fully understand, the insulin will induce peripheral glucose disposal, like in the muscles. So that will basically take the blood glucose out of circulation because of the insulin, and then the ketones also tend to enhance insulin sensitivity. So after about two or three hours, a lot of people will get a headache if they don't combine the ketones with like food or something like that, and it's not a good situation to be in because your hype, your ketone levels are low and your blood glucose is low, so your brain is kind of having an energetic crisis. So that's why people need to be you know kind of that could be. And also, another thing to add is that many of the more potent ketone esters on the market are one,3-butanediol. 1,3-butanediol is a di-alcohol. It's a glycol molecule that has a mild narcotic effect and they're selling it, like you know, as an alcohol replacement because you get buzzed off of it. And my concern is that if you have, like elderly population, if you have a well-meaning parents or children who want to give their parents like a ketone, you know, supplement to basically, you know, because their parents are older and they consume this, then that could make them fall. That could. You know. You do get buzzed off these things.

Speaker 2:

I've I've probably consumed more exogenous ketones than anybody on the planet. I mean, I was experimenting with this stuff back in like 2008 and nine, so I'm aware of, uh, and even in a healthy person like me, if I consume 50 grams of one three butane dial man, I feel, like you know, I've had a couple of drinks and that's not a good situation to be in. That's whereas a ketone electrolyte formulation I use ketone uh, keto start Uh. I for MCTs, I use a product called keto brains. Quest nutrition makes a a ketone MCT powder. So you can. All you need to do is take relatively small dosages of these and you could get therapeutic levels of ketosis, meaning that an elevation of ketones that have been shown in cell-based systems, animal models and in humans to have beneficial effects. So we're talking about one to two millimolar. You do not need to get to two to three to five millimolar, unless you're, like you know, an Olympic athlete or a military diver or something like that.

Speaker 1:

In my opinion, yeah, you mentioned before one last thing, and I don't know if you even are allowed to talk about it, but you mentioned ketones for the military. Is that mainly for diving applications or yeah, yeah.

Speaker 2:

So that's actually what got me interested in this many years ago, more than 10 years ago. So ketones prevent seizures and CNS oxygen toxicity is a grand mal seizure. So the limitation of hyperbaric oxygen therapy and the limitation of how far we can dive underwater using a closed circuit rebreather is oxygen toxicity seizures. And we've tried many different anti-epilepsy drugs and the ketone esters which we tried, especially if we formulate it with MCT, can prevent oxygen toxicity seizures better than any anti-convulsant drug that we have. So this was some of the research that I did and that actually convinced me that even in the context of extreme oxidative stress by extreme you know levels of oxygen, partial pressure of oxygen in the brain 2000 milligrams per. You know 2000 milligrams per milliliter of oxygen in the brain. So this is the normal PO2, like in tissues, it's something like in the brain, it's like 10 to 15. And in like tissues is something like in the brain, it's like 10 to 15. And in like, you know, in the muscle it's maybe like 120, 130. So millimeters of mercury, so 2000 millimeters of mercury if you're exposed to, for example, like three atmospheres of oxygen. So that creates a lot of oxidative stress and the oxidative stress disrupts mitochondrial function. The ketones preserve mitochondrial function even in the face of this extreme oxidative stress disrupts mitochondrial function. The ketones preserve mitochondrial function even in the face of this extreme oxidative stress. So it got me thinking that if it can do this in this animal model that we study at the Hyperbaric Lab, then it has broad implications for other neurometabolic diseases, for other age-related dementias, just by energizing the brain and helping the mitochondrial function, even in the face of like oxidative stress and inflammation, which we were studying. So yeah, so we have I'm I'm on a clinical trial, the co-investigator of a clinical trial at Duke university where they have an amazing environmental hyperbaric facility there where they put subjects into ketosis with ketone supplementation and when they're in ketosis they are using a simulator.

Speaker 2:

So they do like experiments where they're exercising. You know there's a line going. You know they have a central line going through the wall of a chamber to do like real-time blood gases and metabolomics and all this stuff. So yeah, we've moved the animal research into human clinical trials at Duke University and there's a couple, two different clinical trials looking at that. So you know, the next thing is to, like you know, move it into the space frontier. So I've been involved in different projects with NASA Extreme Environment Mission Operations, which is the analog for space training. So we think that these ketones really have the potential to shine in extreme environments, and that's a big part of the research that I do.

Speaker 1:

Wow, this is such a fascinating area of ketones and ketogenesis and ketogenic diets and all you put on a great conference every year on metabolic health that might appeal to people. It just happened in Florida Next year. Is it going to be in Florida again about the same time?

Speaker 2:

Good question. Yeah, we are regrouping and seeing where the next venue would be West Coast or East Coast. Yeah, it's called the Metabolic Health Summit and you can go to metabolichealthcesummitcom and under the Metabolic Health Summit is the Metabolic Health Initiative, where there's an ACCME accredited medical education platform. That people. But yeah, the Metabolic Health Summit was amazing.

Speaker 2:

We have people that talk about cancer Walter Longo talked a little bit about that Neuroscience, cancer biology, metabolic psychiatry. So Christopher Palmer and Georgia Ede and Matt Bazuki and many others, you know, talked about this in Campbell. And then we also have a human optimization, which was the last day, which just talked about, you know, optimizing human performance and longevity. So, and we try to invite sponsors that can actually have something to offer to the community, whether it's like a particular product, it could be a food product or an app or a medical device. So we try to synergize, like entrepreneurs, with clinicians and with basic science researchers, so everybody can come away with something, something very unique experience. Yeah, and thanks for mentioning that and we are gearing up now. So just stay tuned on the Metabolic Health Summit website and we'll make an announcement pretty soon about the next event.

Speaker 1:

Great, and how can people follow you on social media and your website also? Could you mention that? We'll put it in the show notes also, but maybe now.

Speaker 2:

Yeah, I'm pretty searchable, dr Dom D'Agostino, university of South Florida. But I'm on Twitter, I'm on Instagram, facebook, linkedin, so search for me there. Phd Downwing Diagnostics, phd. And then my website is which I have the links there ketonutritionorg ketonutrition all one word, org. So we have a blog on there that covers many topics that we discussed. There's a lot of resources, doctors that practice, you know therapeutic ketosis. You know a wide variety of information I think could be helpful for your listeners.

Speaker 1:

Well, great Well. Thanks so much for taking some time to spend with us today, Dom, and also thanks so much for all the great work you're doing.

Speaker 2:

It's great to connect, thank you. Thank you for having me Appreciate it.

Speaker 1:

It's great to connect, thank you, thank you for having me Appreciate it. I want to thank Dr Dom D'Agostino for joining us today and sharing his amazing knowledge of ketosis and ketogenic diets. Remember that Dr D'Agostino is giving a bonus to our VIP pass members, so if you haven't claimed your VIP Pass that allows you to access the recordings, the transcripts, the MP3s and, of course, our must-have bonus package, you can get it now by clicking the button on this page to upgrade before it's too late. Remember when the event's over, the recordings and all the bonuses go away. So make sure you claim your VIP Pass before it's too late.