98: Ketosis and Ketones with Special Guest Dr. Dominic D’Agostino

Transcript of Episode 98: Ketosis and Ketones with Special Guest Dr. Dominic D’Agostino

With Dr. Daniel Pompa, Meredith Dykstra, and special guest Dr. Dominic D'Agostino.

Learn about how to overcome keto plateau & keto stalling here.

Meredith:
This is episode 98. Here we are, almost 100.

Dr. Pompa:
Together.

Meredith:
We are together. We are in Pittsburgh. Dr. Pompa has joined us in the office, so it’s very fun. I don’t know, this is maybe the second time since we did a recording that we’ve actually been on the same screen sharing it. It’s fun to have you here and to be together to record.

We have a very special guest for you today, Dr. Dominic D’Agostino. Before I introduce him, I’m going to read his bio, and then we’re going to learn a little bit more about Dr. Dominic. Is that what we call you, Dr. Dom, Dr. Dominic?

Dom:
Dom is great, yeah.

Meredith:
Dom, okay. We’ll hear more about Dom’s work and all the amazing, amazing things that he’s doing in his lab. We’re going to be talking about ketosis, about using exogenous ketones. We’ll explain what those are if you don’t know. It’s going to be an amazing episode. Let me get started here and tell you a little bit more about Dom.

Dr. Dominic D’Agostino is an assistant professor in the department of molecular pharmacology and physiology at the University of South Florida, Morsani College of Medicine and also a senior research scientist at the Institute for Human and Machine Cognition. The primary focus of his laboratory is developing and testing metabolic therapies including ketogenic diets, ketone esters, and natural and synthetic molecules to target metabolic processes.

His research also explores the use of these therapies for a broad range of disorder linked pathophysiologically to metabolic dysregulation including seizures, neurodegenerative diseases, genetic diseases, and cancer. D’Agostino’s laboratory uses in vivo and in vitro techniques to understand the physiological, cellular, and molecular mechanism of metabolic therapies.

His research is supported by the Office of Naval Research, the Department of Defense, private organizations, and foundations. Very impressive bio. So excited to have you here, Dom. Welcome to Cellular Healing TV.

Dom:
Thank you for having me. I appreciate being here.

Dr. Pompa:
Yeah. It’s very impressive work you’ve done, Dominic. I found your work, of course – I read a lot of the studies, and love tracking down the person at the heart of them. First of all, thank you for your work because it is changing lives. It’s making a difference. I’ve watched the ketone diet and ketoadaptation change many lives. Your area of neurodegenerative work, neurodegenerative diseases, I tell you, that’s where I just see it flourish. We have doctors around the country that are trained in ketoadaptation, ketogenic diets, and they thank you. Believe me.

Dom:
I think you for implementing it and building a team of people who understand this, and most importantly, connecting with the patients. Really, disseminating this information is really the most important thing. I could spend all my life in the lab, but if it’s not being implemented and information is not getting out there, then there’s no use.

Dr. Pompa:
Yeah. We appreciate that. One of the questions we had right away when we sat down is – Meredith goes, “How did he get into this?” How does someone get into studying ketosis? I’m sure our audience is thinking the same.

Dom:
Okay. I’ll take a step back. In my undergraduate, I studied nutrition and biological sciences with the intention to go to medical school. Also, kind of with that in mind, I wanted to do some research in a lab, and I chose to work under the research dean of Rutgers University. She was doing some fascinating work on the neural control of autonomic regulation, how our brain responds to low levels of oxygen and adjusts cardiovascular and respiratory output as a function of oxygen. It gave me the opportunity to study neuroscience, but also studying the physiology through which our brain controls, how our brain controls our respirations.

That gave me a pretty good foundation in medicine and understanding some things. I had the background in nutrition already. Then my postdoctoral work was actually working with the Office of Navy Research and working on the other end of the spectrum, which is not low oxygen, but what happen when you’re exposed to high pressures of oxygen in the context of using a oxygen rebreather, which is really specific to Navy SEALs and the special operations community. When you’re using a rebreather underwater, the advantage is that there’s no bubbles. There’s a stealth component to using this technology.

One of the drawbacks is that you’re breathing 100% pure oxygen in a closed circuit rebreather. A major drawback, a disadvantage, is that you have the potential for seizures. If you need to go deep, if you’re taking on fire, you want to evade the enemy, you go deep with this instrument, this equipment. Breathing high oxygen, is a stimulant to the brain. In that way, it can be used sort of therapeutically for different disorders with hyperbaric oxygen therapy, which is about 2.5 atmospheres, max. If you go down farther than that in terms of atmospheres pressure, then the overproduction of oxygen free radicals disrupts brain energy metabolism in a way that triggers a seizure. A seizure underwater could be fatal, and it’s going to end the mission for sure.

If we could lift this limitation, then we could make the physiology of extreme environments much more safer, and we can increase the capability of the war fighter. Understanding this could also enhance and increase the capability of hyperbaric oxygen therapy. The protocols that are used now – hyperbaric oxygen therapy can be used – now there’s 15 FDA-approved applications that your insurance will cover. Then there’s a lot of off-label applications of hyperbaric. The limitation of the pressure is CNS oxygen toxicity.

Dr. Pompa:
Is that where ketosis comes in?

Dom:
Yeah.

Dr. Pompa:
They can tolerate more? Explain that.

Dom:
Yeah. That’s what I’m going towards. Oxygen toxicity is a tonic clonic seizure of CNS. The military has spent a lot of time and effort looking at things like antioxidants and anticonvulsant drugs, but to get the efficacy of an anticonvulsant drug, it needs to be used in a dosage that’s essentially sedating. You don’t want to sedate a Navy SEAL and send him off to a mission where he’s got to dive.

In the process of looking at the cellular and molecular mechanism with all the tools we have in the lab, I realized that this is – the breakdown in brain energy metabolism was really what was leading to the seizures. I just kind of stumbled upon the ketogenic diet because I was searching, “What do people do when drugs fail for seizures?” I saw that the standard of care for drug refractory epilepsy, drug-resistant epilepsy, was the ketogenic diet. There’s also vagal nerve stimulation. The ketogenic diet had a remarkably good track record.

When I pulled all the literature, and I spent a few weeks reading it, I was really blown away. I was like, this is a highly – a grossly underutilized metabolic therapy that had tremendous implications.

Dr. Pompa:
How many years ago was that that you started researching it?

Dom:
I discovered it in 2008, I believe. I actually knew some people around me, one of them is Mike Dancer. He was in Europe at the time and connected with me. I recommended that he try it because he was going to have brain surgery for temporal lobe epilepsy. It literally almost cured his epilepsy. It stopped. He went from being homebound to having his life back again. I just was reading one paper and one report after another, and I contacted the program officer in 2009, I believe.

Within a year or two after that, I was able to write up a proposal, and dig up enough information, and kind of get all the logistics in place to run an actual study in the lab. About 2010, I was really full-force in the lab, running seizure studies, looking at the mechanisms of oxygen toxicity. The program officer at the time was not really interested in the ketogenic diet because this – using a high fat, low carbohydrate diet.

The low carb diet, I could kind of get him onboard with that, but when you talk about a high fat ketogenic diet, there was a little bit of pushback. It was just like, “Can we achieve this same elevation of ketones? The ketones seem to be playing a neuroprotective role. Can we do that? Can we circumvent the diet and develop a ketogenic diet in a pill?” In parallel to our ketogenic diet research, I was also working on developing various forms of exogenous ketones, ketone supplements.

Dr. Pompa:
Exogenous ketones.

Dom:
Yes – and esters and ketone salts. We would develop these things and then test them individually to find out which ones were most potent and which ones had the greatest potential for therapeutic efficacy. There were a few particular ketone esters that had the most anti-seizure, anticonvulsant effect relative to some other things that we were trying.

They are the substances that we’ve been focusing on and advancing their use as far a safety, toxicology, pharmacology. We’re doing all this work for the FDA and tracking them as a medical food for very specific neurological disorders, but also for the special operations community, where they have first choice or first dibs, if you will, of the highest potency ketone products. These are more synthetically based or synthesized ketone products.

Then there’s naturally derived ketone products like ketone salts, like a mineral salt. Sodium, potassium, calcium, magnesium, and even various amino acids can be bound to ketones, namely beta-Hydroxybutyrate. These can be developed in a way that’s somewhat palatable and formulated with powdered, medium-chain triglycerides. We’re testing these things individually, and now we’re in the process of formulating them together to get a balanced electrolyte and amino acid formulas. You got to do that – what looks good on paper does not always pan out in the person’s stomach or their palate. You got to formulate it in a way that tastes good and formulate it in a way that’s tolerable to your GI.

Dr. Pompa:
We have a lot of questions about exogenous ketones, meaning ketones you take as opposed to going into ketosis. Before we even get there because that is some of the questions that we had had, and we had a lot of people write in about the exogenous ketones, probably knowing that your name was connected to studying some of these. I think it’s interesting that you work with these – right now, I don’t even know if we can say where you are. Can we say where you are right now?

Dom:
I’m in a special operations community.

Dr. Pompa:
Special operations, we’ll leave it –

Dom:
Uh-huh – at a base right now. Yeah. Yesterday, I couldn’t connect because I was kind of – the signal would be scrambled.

Dr. Pompa:
Exactly. Right. You’re working with all these special ops, right, whether it was the SEALs, the Rangers. That’s really an amazing interest because they’re obviously seeing the benefits of ketosis. Dominic, you saw the benefits of ketosis beyond even seizures, in neurodegenerative conditions, as we did in our world, dealing with people with unexplainable illnesses and realizing that, wow! Ketones have a major effect on so many different conditions. Why is that? Why is ketosis such a powerful tool?

Dom:
I think there’s numerous reasons for that. We know from a decade or – I’ll say a century of – basically almost a century of using the ketogenic diet for drug refractory epilepsy. The etiology of epilepsy is largely unknown for the most part, for most forms of epilepsy. What we do know is that there’s abhorrent neuronal activity. You could say that impaired brain energy metabolism is really pathophysiologically linked to pretty much all neurodegenerative or neurological diseases. Right?

Dr. Pompa:
Yeah, yeah.

Dom:
The data was pretty clear that when a person gets on a ketogenic diet, numerous pathways – I would say there’s 20, off the top of my head, really, that are kind of brought back into homeostasis. If your gaba level is low and your glutamate is high, if you have excess reactive oxygen species, if your certain brain energy metabolites, like alpha-Ketoglutarate, succinate malate are low, the ketogenic diet is what we call anaplerotic. It actually feeds into the Krebs cycle and elevates these Krebs cycle intermediates. Alpha-Ketoglutarate is actually a precursor for glutamate. Glutamate is actually converted into gaba, and gaba is an inhibitory sort of neurotransmitter that maintains neurological homeostasis.

The ketogenic diet does some key things. It converts more of a neurotoxic substance – or signaling substance, glutamate, which can be neurotoxic at high levels. It shuttles the excess glutamate to gaba, which kind of makes us feel calm.

Dr. Pompa:
Yeah. Glutamate, just for the watchers, is the most excitatory neurotransmitter, whereas gaba’s the most inhibitory. Am I right on that?

Dom:
Yes.

Dr. Pompa:
Just for the people watching – we have doctors and public watching. What you’re saying is basically, it brings balance to brain chemicals. It brings balance to energy in how the – matter of fact, it improves cellular energy, which has an effect on all these processes, how your brain works, how your metabolism works.

Dom:
Yeah.

Dr. Pompa:
That’s what you’re saying. It brings homeostasis, balance to basically every process in the body that can drive inflammation, which obviously causes a lot of diseases. It downregulates inflammation, brings balance to these chemicals. Is that simply –

Dom:
Yeah. That’s perfect. That’s much better put. Yeah, you hit on a couple good topics. By restoring – bringing energy metabolism and these intermediates, it also feeds into the production of neurotransmitters, which also is put back into balance, and neuroinflammation, too. We looked at a variety of neuroinflammatory – or just systemic inflammatory pathways. Many of these are suppressed by nutritional ketosis, specifically by beta-Hydroxybutyrate. We have a Nature Medicine paper showing that it –

Dr. Pompa:
Dominic, just so people listening – beta-Hydroxybutyrate is the most abundant ketone that’s formed. When we break that down, we make ketones, and beta-Hydroxybutyrate is one of these ketones that we make that we know makes the brain work better, turns off genes, etcetera.

Dom:
Yeah. That’s right. When I got into this in 2010, the signaling properties of metabolites, specifically ketones, were not even discussed, really. We just understood ketones as an energy metabolite, something that could more or less replace glucose as a brain energy fuel.

Now, you have a science paper showing that it functions as – on gene expression. Through epigenetic regulation, it can enhance our antioxidant capacity. It can have a profound effect at decreasing inflammatory pathways that are chronically over-expressed in age-related diseases and even many cancers. We’re looking at a dozen or more different signaling pathways that ketones are working through and not just – it’s much more than just a metabolite.

Our research is going in that direction, and we’re also using what’s called metabolomics. We’ll collect blood, and we’ll collect tissues from animals that are on a ketogenic diet, but also on ketone supplementation. We can look at all the metabolic pathways by looking at the metabolites. We have a firm understanding, specifically, of what’s being altered, what precursors are being generated from being in nutritional ketosis. That gives us greater insight into the benefits of ketosis.

Dr. Pompa:
Yeah.

Dom:
Of course, there’s a lot of pharmaceutical companies interested in this data because if they can identify specific things that are being regulated by the ketogenic diet, then they can make a druggable target. I can just tell you that the big pharmaceutical companies have contacted me, and they want to know – they’re not even shy about it. They’re like, “How can we create a – what are druggable targets of the ketogenic diet? Can you come to our institution, our facility, and give a talk just on all the different pathways that we can create drugs for? We realize that this has tremendous therapeutic potential. How can we make this into a drug?”

It’s going to be hard because there’s a dozen or 20 or more different major pathways that are being altered kind of synergistically with nutritional ketosis.

Dr. Pompa:
Dominic, when we look at cultures in history, all of them utilize ketosis at different parts of the year, the Hunzu people [00:19:03] we go down the history. Ketosis is something the body naturally goes through. I just want people to understand listening because people listening have different things, energy problems, conditions, weight loss issues, hormone issues.

What you said is so key. It’s like ketones go up. Okay. They stabilize glucose and insulin, which is – how many diseases right there does that affect, including anti-aging? That’s a benefit. It turns off bad genes. People that are watching this, a lot of things that your genes are expressing is why you don’t feel well. You’ve made dietary changes. You made a lot of things in your life. However, these genes are still turned on. What you’re saying is ketones go in and turn off those switches, literally change what our genes are expressing.Dominic, that happened to me. When I was in ketosis several times, I know I had certain chemical sensitivities. Genes were turned on, certain pathways. I felt them. I watched them downregulate, and I know it was the ketones just turning off those switches. That’s amazing research.

Dom:
Yeah. There’s no limit to – I get emails every day. There’s one NIH investigator contacted me and had a rare genetic disease. The only thing that worked for her was the ketogenic diet. She’s a drug researcher and was like, “I want to steer the ship of my lap in this direction and start studying the ketogenic diet because it worked for me.”

Another person at more or less an Ivy League institution had Graves’ disease, a big researcher, and contacted me, and said ketosis was the only thing that worked for her. We have studies going on now with things like glucose transporter type 1 deficiency syndrome. This is a fairly rare genetic disorder where you have a persistent molecular pathology that’s largely silenced when one is kept in nutritional ketosis. This disorder, glucose transporter deficiency, prevents the brain from getting glucose via deficiency in the GLUT 1 transporter.

When these kids and adults that have this disorder are maintained in nutritional ketosis, it provides an alternative source of energy to the brain. It’s the most powerful way to stop their seizures and treat the motor function deficiencies that’s associated. It is the standard of care. That’s where ketone supplements kind of come in, to maintain these kids. If the kids are out of ketosis, the symptoms are severe, and they’re in a wheelchair. If they get into strong ketosis, they’re like a different person.

We’re working on some of these pathologies that are highly responsive to nutritional ketosis. One that just kind of popped up is Angelman syndrome. The leading investigator of this is Ed Weeber at our university, the University of South Florida. The Angelman syndrome community has contacted us and him and said, “When we put our kids on the ketogenic diet, it works better than any drug that’s out there.”

Meredith:
Heard of it.

Dom:
What’s that?

Meredith:
What is the syndrome?

Dom:
Oh, the syndrome is primarily drug-resistant seizures and really bad motor function issues, so coordination is really impaired. It’s a genetic disorder where there’s a deficiency or an abnormality in what’s called the housekeeping gene in the brain. It leads to kind of a host of neurological and physiological symptoms. As far as I know, I think the ketogenic diet, from the literature, has been the most potent therapy for this.

We’ve did a mouse study where we looked at drugs, and we looked at the diet – actually supplements, ketone supplements. It had a remarkable effect. The foundation is actually more interested in putting funds towards developing ketone therapy instead of a drug therapy for this disorder. We’re working really close with them. That’s going to be one of the – because it’s a rare disorder, it’s more likely that we can get approval for using ketones for this. That may set the stage for a lot of other pathologies.

In addition to the special operations community, where we want to use it for protecting, neuroprotection in under-extreme environments and also enhancing cognitive and physical performance, there’s that sort of research. I think it’s really great to be able to leverage the research that we did for the military and to use that same research as a foundation for these rare neurological diseases, and even Alzheimer’s, and Parkinson’s, and ALS, or things.

Dr. Pompa:
It makes the brain work better, heal faster, and you said something. The special ops using it for athletic performance and –

Dom:
Yeah, absolutely. That was the original application of ketone esters, which in the work that was funded by DARPA, and this goes back more than 10 years, about 15 years, that was – one of the original applications was physical performance. It has proven to enhance physical performance above and beyond what was expected even in elite level athletes.

Meredith:
Exciting!

Dr. Pompa:
I said before we got on the show that every summer, I go into ketosis because as a cyclist, I become bonk-proof, literally endless energy. My body gets so efficient in utilizing fat for energy and ketones for energy that I can go and go and go without eating and without losing energy, really, is the important part of that.

Dom:
Yeah. That’s cycling and running, too, or mostly cycling?

Dr. Pompa:
I’m not a runner.

Dom:
Yeah. I don’t run, either.

Dr. Pompa:
I actually hate running. I’m genetically really gifted at it, just do not like it, but I love cycling. Yeah. My performance just goes up. I had said to you, also, that Professor Stephen Phinney – Dr. Phinney came to Park City, where I live, and he lectured to a group of endurance athletes who are carbotorians. These people, they’re doing the high carbohydrate endurance diet, if you will. His message – I don’t know. It was received by some, but I could tell there was a lot of resistance with people who couldn’t get how you could be high performance on a keto high fat diet and still run long-distance and cycle long-distance. I think we had one question from one of our doctors who sent it. Go ahead and give that, because I don’t want to –

Meredith:
Yeah. I’ll put this in. This is from Tammy Stewart. She’s an amazing doctor, well, practitioner. We’ve heard it before, but why would some people not lose weight in ketosis? She’d like to hear, too, more reasons on why people have a hard time getting into ketosis.

Dom:
There’s a variety of reasons for that. I think someone needs to work with a doctor or a nutritionist that’s sort of savvy in the ketogenic diet. I think it’s really important to – before anyone even starts the ketogenic diet, there’s certain things that they need to do. They need to know that they have support of the people around them. They need to clean their house out of all the different foods that are potentially non-ketogenic. They need to invest in some readily available technologies that are out there from a urine ketone strip to a blood meter to maybe even – we’ve been experimenting with the ketone breath analyzer.

Dr. Pompa:
Yeah. We’ve been experimenting with that, too. Her question, Dominic, is specific for – hey, we’re measuring the blood ketones with a particular patient/client.

Dom:
Okay.

Dr. Pompa:
They’re in there saying, “Hey, I’m under 50,” and even under 30, maybe even under 20, and they’re still not able to see the higher numbers. I think that was what she was focused on.

Dom:
Oh, not higher ketone numbers or – okay.

Dr. Pompa:
The person, the patient or something not getting into ketosis even though they seem to be doing everything perfectly, and they’re not getting the blood reading.

Dom:
Yeah. The more you follow the ketogenic diet, the easier it gets and the more benefits you derive from it. It takes awhile. The keto-adaptation phase that Dr. Stephen Phinney may have talked about, one of the processes – not only does it upregulate the transporters for your tissues to use ketones for fuel, but you’re also upregulating the ketolytic or ketogenic enzymes in your liver.

By following a ketogenic diet, you’re enhancing liver ketogenesis – the process of liver ketogenesis over time if you’re doing it right. You will, over time, probably be making more ketones. Most people do. I know me, for example, it was really hard in the beginning. It took about at least three to four months to reliably see even one to two millimolar on the blood meter.

Now, if I take a day, and I kind of get out of ketosis for one reason or another, by middle of the day the next day, I can be quickly back into ketosis. That was not the case. I think over time, there’s maybe epigenetic effects that – where you have enhanced mitochondrial biogenesis, enhanced mitochondrial efficiency, and an increase in ketone production through enhancing the enzymatic pathways.

Also, for people that are using this for weight loss, a lot of people think if they follow a ketogenic diet, “I don’t need to count calories. I don’t need to count macros.” A lot of people are like, “No, I’m not” – I communicate a lot with the fitness community where they use, I guess what it’s called, If It Fits your Macros, IIFM. If It Fits your Macros is like you work with a dietician, and they assign you – “You had 200 grams of carbs today, 150 grams of protein, and just stick with that. Eat whatever food you want, but stay within that macro-nutrient range,” sort of like a Weight Watchers sort of thing, where it’s points. There’s an app that’s popular, If It Fits your Macros. That’s used by a large population – a large part of the fitness community.

When people get on a ketogenic diet, they think that they can throw out this whole idea of counting calories or anything. They really need to – if you’re eating something like macadamia nuts, or cashew butter, or I make ketogenic ice cream at night. If I’m really hungry, I can shovel a lot of that down my mouth and get a big calorie load. Whenever you get a calorie surplus, those calories are going to need to be stored. The thing with the ketogenic diet as it works for most people is that it inadvertently causes someone to revert back to normal calorie intake.

Dr. Pompa:
Absolutely! Absolutely!

Dom:
Fluctuations in insulin and glucose will stimulate cravings that will trigger you to binge, and those excess calories are damage, and they cause pro-inflammatory spikes in your body. When your appetite is controlled with nutritional ketosis, you’re much less likely to fulfill those cravings, and you kind of just revert back to a healthy way of eating, where your appetite is controlled. You eat to sustain energy and not eat to fulfill some kind of psychological or physiological deficiency.

Dr. Pompa:
That’s what we notice. When people go into ketosis and their body works correctly, there’re certain things that are released when you break fat down that actually go, “I’m not hungry.” When I go into ketosis, I’m going, “Gosh, I forget to eat.”

Dom:
Yeah.

Dr. Pompa:
I always say, “You can’t get on a caloric restriction diet just pushing food away because eventually you fail on a diet, caloric restriction that way.” When you go into ketosis, when things are working correctly, you automatically eat less. However, some people, like you said, whether it’s emotionally, they don’t automatically eat less for whatever reason. Therefore, they’re still taking in a lot more food than their body actually needs, and then it wouldn’t work for weight loss in that case.

We always say, and we discuss this with Seyfried, is that ketosis or fasting create restriction, and eventually, the body starts to do the right thing. Eventually, people go, “Oh gosh. I’m such an efficient fat burner,” that they will [00:32:31] we get all the benefits it seems. We had noticed for people who aren’t getting into ketosis for on three, four months, and they’re still not able to break through. We have broken them out of the diet, went back to a healthy – I would say healthy, higher carbohydrate diet, still considered low in America. Then three months later, go back into it, and boom! All of a sudden, they go right back into ketosis. I think you’re right. I think something genetically shifts, and they’re able, all of a sudden, to get back in.

Dom:
Mm-hmm. Yeah. The first time you try the ketogenic diet for most people, it’s really hard to adapt. There’s a lag time. Your brain goes through what I call glucose withdrawal. If you transition to a ketogenic diet, your brain is like, “Where is my glucose?” It sends a stress response to your sympathetic nervous system. Your sympathetic nervous system, your adrenaline gets released. Your cortisol goes sky-high, and that’s a pretty big stress response.

I’ve seen this in women, especially, because I think women’s hormonal systems are much more sensitive to depravation of glucose and carbohydrates. They kind of get a pretty big stress response unless they’re a hardcore athlete, where they’re sort of balancing in and out of ketosis anyway from super prolonged exercise. That’s the level of a tri-athlete or iron man fitness athlete. Men, too, that engage in – even the high carb community that’s transitions to a ketogenic diet has a pretty easy – easier job doing that, some of them, because they’re kind of bouncing in and out of ketosis. You have this phenomenon of post-exercise ketosis if your glycogen is depleted.

When you take a sedentary person who has really high glucose, insulin, inflammation, and transitioning them completely devoid of carbohydrates, they’ll have a lot of issues that they kind of have to go through. I think that’s where exogenous ketones may come into play. Also, when they’re in nutritional ketosis, you do have – not only is glucose and insulin kind of controlled, but neuropeptide Y, which actually goes up when we fast, is regulated in ways. There’s a lot of neurological hormones –

Dr. Pompa:
Wait a second. Most viewers don’t – what neuropeptide Y?

Dom:
It’s actually a neuropeptide that’s involved – that’s actually released when we fast. I’m interested in it because it has anticonvulsant effects. There’s certain receptors and pathways in the brain that are activated by neuropeptide Y. The literature’s not really clear on exactly what it does, but from a pharmacology point of view, it tends to hyper-polarize the membrane potential neurons, and it keeps the brain sort of in a – it helps regulate homeostasis in the brain.

It has some interesting effects on appetite regulation, too. I think another thing to acknowledge is that the ketones themselves have a satiating effect and help to control appetite. It helps to boost and maintain brain energy metabolism. If you keep the brain happy by giving it fuel, it’s going to say – it’s not going to have that stress response, and you’re not going to get these cravings. If you deprive it of its fuel, it’s going to go into stress response, and you’re going to be seeking high – hyper-palatable foods in the form of salty, very sugary foods to mitigate the stress response. If you’re feeding the brain ketones, it has a steady fuel supply.

I think some of the – a large part of the glucose withdrawal and issues that people have in transitioning to a ketogenic diet, much of that could be mitigated with ketogenic supplementation. Coconut oil would be the simplest, there’s a powdered MCT that I really like, to the more powerful exogenous ketones that are on the – that are soon to be on the market.

Dr. Pompa:
Let’s talk about that. Let’s talk about, now, exogenous ketones. We put people, like I said, in ketosis, ketoadaptation. Like I said, in a healthy person, it takes two or three weeks. You’re telling us that these people that have trouble breaking through, we have utilized pulling them out of it, eventually moving them back in. You’re saying, “Hey, it’s just time.” You’re right. I agree with that. We’ve found that, and we’ve used our diet variation, where we – switching people’s diets around to break them in later, and it seems to work.

Let’s talk about these exogenous ketones. We’ve got a lot of questions about them. Meredith, you have them there. First of all, a question that I have. Ketones are a byproduct of breaking fat down. Your body makes these ketones to make up the glucose – the energy at the cellular level. When we put someone in ketosis, we’re cutting their carbohydrates down so much that their body has to start burning fat. It starts utilizing fat more efficiently, and it makes these ketones that the brain can use and the body loves to use. Okay.

We get the benefits. You said them. Turning off genes, balancing energy, all these amazing things for the brain and our body. Okay. If we take ketones, exogenously, we take them, would that shut off that metabolism eventually? Could it? Are there side effects?

Dom:
Yeah, that’s a great question. I think we need to acknowledge that ketones are a calorie-containing food, really, almost like a fourth macronutrient, really. You have fats, you have carbohydrates and protein. I think of ketones as like if you take long chain fatty acids and you chop it up, like you throw it into a wood chipper, you get these small molecules. These are water-soluble fat molecules, I think of ketone bodies. These have the capacity to cross the blood/brain barrier and then maintain brain energy metabolism unlike long chain fatty acids, which are stored in our adipose or consumed in most fat sources.

If we’re in a state of natural ketosis with just strictly the ketogenic diet and we consume a large bolus of exogenous ketones in the form or powerful esters or ketone salts, what you will see – we want to do some respiratory quotient, look at – we’re using a metabolic car. We plan to study this phenomenon. I think you could probably turn down fat metabolism a little bit, but it would be turned down less if you were to consume an equal amount of calories from carbohydrates, absolutely, and protein, even. You can maintain the fat burning process much longer and give your brain a high-energy source.

You may turn down fat metabolism a little bit just because you’re putting energy into the system. Whenever you’re putting energy into the system, any system, you’re going to turn off the oxidation of fats to make those ketones. Your body’s going to regulate that pretty well. It does that pretty well with exogenous ketones. When we take exogenous ketones, our blood ketone levels will get elevated to a point where it causes a very small release of insulin. That small release of insulin nowhere near is what you’d get if you drink a sugary drink or even protein.

That small amount of insulin will start to turn down hepatic ketogenesis. That’s how we actually regulate. When we’re making ketones, our ketone levels get higher with a ketogenic diet. Then we have ketone urea. Then if they get really high, there’s a ketone-induced release of insulin. That will turn down hepatic ketogenesis.

Dr. Pompa:
Okay.

Dom:
I guess maybe an easier way to describe it, if I’m fasting or if I’m on a ketogenic diet, and someone injects insulin into me, that insulin is going to shut off my – that’s going to put me in kind of a bad situation because it’s going to make me hypoglycemic and also turn down my body’s ability to make its own ketones, although there’s a lag time. It’ll take an hour or two.

There was an interesting experiment actually done at Harvard by George Cahill, who is a pioneer in fasting and ketogenic research. He fasted people for 40 days and adapted their brains to being in ketosis. There’s no way you could reproduce this study nowadays because it could never pass IRB. They looked at blood going to the brain and blood coming out. They found that about 2/3 of the brain energy after about 10 days with being derived from ketones. In that state of fasting ketosis, he injected them with 20 IUs of insulin, which would be fatal to most people. The people that were in a fasted condition, they were asymptomatic for hypoglycemia.

They did cognitive function tests, and they even performed well on cognitive function tests. Their blood glucose went down to one to two millimolar, which would give a seizure and a coma for most people, but because their ketones are elevated, they had extreme metabolic resilience against hypoglycemia. They didn’t even feel it. That’s when someone’s in nutritional ketosis or someone’s using exogenous ketones, and they have dips in blood glucose, which causes cravings. It makes you angry and irritable. It shuts down performance. You’re resilient against that. You’re kind of bonk-proof because your brain is being – using another fuel.

Getting back to your question, yeah, it can start to turn down fat metabolism a little bit just because you’re putting more energy into the system, but at the same time, you’re enhancing all the metabolic pathways that allow your body to use ketones for fuel. You’re enhancing mitochondrial biogenesis. You’re enhancing mitochondrial efficiency. You consume ketones. Your ketone levels get elevated and then come back down when you burn them up. If you do that over and over, it’s actually enhancing your metabolic pathways and mitochondria to make you a better fat burner and a better ketone utilizer over time.

Dr. Pompa:
You think the best benefit would be when someone’s adapting. This three-week time when they’re adapting, that’s a better time to take them? Is there–

Dom:
I think so.

Dr. Pompa:
Let’s say you’re just full-blown ketosis, is there a benefit to taking them then?

Dom:
I think, yeah, there’s definitely a benefit in that transition phase.

Dr. Pompa:
Yeah. Right.

Dom:
If someone’s fasting, maybe if someone’s choosing to do intermittent fasting, and they only eat one time a day, like at night –

Dr. Pompa:
We eat 1 ½. We don’t eat breakfast. We do that daily all the time. Go ahead. Finish your point.

Dom:
Yeah. Maybe doing that and further increasing your ketones throughout the day if you need a boost, someone could do that. I think the main application would be transitioning into a ketogenic diet and maintaining – enhancing that compliance. I find the biggest issue with people following the ketogenic diet is compliance due to cravings, due to just that transition period. If they can get through that transition period at about the three, to four, to up to six week mark, they really start knowing the benefits, getting the benefits, especially if they do blood work.

They’ll see their insulin levels are under control. Their inflammation goes down. Their glucose is under control. They’ll see all these health benefits starting to come up. If they want to get – for athletes, a performance boost. You could use a intro workout – pre-workout, intro workout. I just think, in general, that ketones may be – like I said, it’s more than just a metabolic fuel. It’s affecting gene expressions. If someone was consuming them, you could expect that you’ll be activating pathways that are anti-inflammatory. You’ll be activating pathways that epigenetically regulate endogenous antioxidant pathways, longevity pathways, even. These are becoming a focus of the major labs that are looking at longevity now.

There was a paper published in Oncotarget. I think the title of the paper is Beta Hydroxybutyrate, the Longevity Metabolite. It has a elegant – experiments were done in C. elegans, the nematode worm where the original calorie restriction was done using this model. In that model, you get an extension of a life, about 25%, if you calorie restrict the worms, C. elegans. You can mimic that same effect independent of calorie restriction simply by feeding beta-Hydroxybutyrate.

Dr. Pompa:
Wow.

Dom:
You can extend the lifespan. It mimics many of the effects of calorie restriction. I know Dr. Seyfried’s really big on restriction. He’s really big on calorie restriction.

Dr. Pompa:
Yeah.

Dom:
I think maybe when we started originally talking, he was thinking that a lot of the benefits being derived from the ketogenic diet were simply due to calorie restriction. We did some studies showing that it’s more than just calorie restriction; it’s the effects of the ketones. If you are in ketosis and you calorie restrict, you get a two-for. You get a double whammy. You get the benefits of calorie restriction and then the benefits of the –

Dr. Pompa:
Dominic, one of the problems I always have with caloric restrictions, nobody can do it when they’re just saying, “I’m just not going to eat.”

Meredith:
It’s not sustainable.

Dr. Pompa:
It’s not sustainable. However, when you caloric restrict because you’re just not hungry, that’s when people look at the Okinawa people or these people, these groups that live long. They don’t eat much. They’re not eating because they’re going, “I’m just gluttonous. I’m going to push it away.” They eat less because they’re not hungry because they’re efficient fat burners. They’re efficient at utilizing ketones and fat. Really, that’s what I want people to understand. That’s the state to where you’re increasing your life. You’re eating less. You’re caloric restricting. We caloric restrict everyday, but I’m not hungry. That’s because we’re so efficient at fat burning. Obviously, it takes time to get there and utilizing these strategies that we’re talking about.

Exogenous ketones, you feel are most useful in that transition. Absolutely. I could see that, where people are going to fail. Once somebody adapts, is there still a benefit to taking it? I also want you to say how often should people take it? How much in a day? Also, which ones do you like? There’s three questions.

Dom:
Mm-hmm.

Meredith:
And long-term risks. They were wondering about that, too.

Dom:
Long-term risks, okay. Okay. That’s a lot of questions.

Dr. Pompa:
Sorry, man. I’m so excited about this.

Dom:
I know. I know.

Dr. Pompa:
I’m coming out of my skin because I’m thinking, “Gosh, if I don’t get these questions answered, I failed my viewers.”

Dom:
As you know, I’m a big fan of the ketogenic diet. I follow the ketogenic diet, too. I just like eating that way. I like the foods that are part of the ketogenic diet. I would more or less call it a modified Atkins or modified ketogenic diet because instead of 90% fat, I’m probably getting about 60% to 75% fat.

Dr. Pompa:
That’s what I do, as well.

Dom:
Yeah. Okay. That would fall under – that’s away from the clinically used ketogenic diet, and that falls in the camp of the modified Atkins or modified ketogenic diet. From a clinical perspective, that’s being advanced by Dr. Eric Kossoff at Johns Hopkins – has been using that diet very successfully for seizures and whatnot. He’s written some elegant reviews on that, just showing the literature, showing that you don’t have to be this strict. You don’t have to necessarily be on a 90% fat diet. That was the original Johns Hopkins protocol.

He’s having very good success with a modified Atkins. I think that’s really what athletes will benefit more from because it’s higher in protein. We know we do need protein for rebuilding after workouts to maintain lean body mass. In the context of that diet, your ketones are going to be a little bit lower than the standard ketogenic diet. Instead of three or four, you’re going to be hitting one or two.

Dr. Pompa:
That’s right.

Dom:
You could bump it up – from a clinical scenario, you could bump it up to three or four millimolar. I, personally, feel best between one and two millimolar. If I take exogenous ketones and I start getting up above three to four to five, I just don’t feel – I start to feel a little loopy. I get a ketone euphoria or something, especially if I’m sitting at my desk.

Dr. Pompa:
No, no. I have to say that. That’s true. I only got it when I took the exogenous ketones. I was probably around one or two. I intermittent fast daily, so I’ll get high ketones even when I’m not in ketosis towards the afternoon, right?

Dom:
Yeah.

Dr. Pompa:
I took some exogenous ketones, and I said, “Gosh, I almost felt a little loopy,” just like you said. I felt something. That’s what I felt. I didn’t realize. I didn’t test my ketones at that point. It’s happened twice to me. That’s what it was.

Dom:
It could range from – even if I take MCT, a lot of it, I start to get a little bit anxious. It’s sending so much energy to my brain – especially if I’m in kind of a well fed or kind of a well-rested situation.

Dr. Pompa:
I guess that’s important.

Dom:
Sometimes, if I’m traveling overseas and missing a couple nights of sleep and sleep deprived, the ketone supplements really help in the context of that situation. I was talking with the special ops community, and they’re really big on using modafinil or Provigil, which is kind of like a stimulant or amphetamine, dexamphetamine. The ketones actually are a natural way that they think they can preserve their cognitive and physical performance under conditions of missing a few nights of sleep. They do their operations at nighttime, so a lot of the guys are sleep deprived.

I think in the context of sleep deprivation and stress, ketones can really shine. I use them more in that scenario, but I don’t really – besides MCT. I’ll put MCT in my coffee. MCT powder, I use. Quest Nutrition makes a really good one. I actually helped test that product, and I like it a lot. I will use ketone supplementation. I tend to eat a small – relatively small breakfast, high protein, ketogenic, high fat breakfast.

Dom:
I don’t eat for 12 hours. Yeah. What’s that?

Meredith:
What was that? Your breakfast. We’re curious.

Dom:
Yeah. It’ll vary. I went a couple weeks just doing one meal per day, and I started losing weight, about one pound per week. I just can’t maintain my size and my strength. I don’t desire to be really big. My weight is about 100 kilograms. I feel that’s a good weight for me for my height. It starts to drop below that if I start to do the one meal a day intermittent fasting.

Dr. Pompa:
I do one and a half to two, and it’s my sweet spot. I get about 18 hours, maybe, you know what I’m saying, of fasting, maybe 19. That’s my sweet spot. Yeah, you have to find your sweet spot.

Dom:
Yeah. That’s what I find, too. I’m traveling, so – actually, the hotel had breakfast, and I could have ate here, but I had sardines packed in olive oil, and I had oysters packed in olive oil. I have little bags of spinach that I brought, so I just put that in the thing and ate that. I had to wake up real early for a meeting, so I just downed that. That was my meal.

In the evening, I’ll have a fish salad with avocado. I’ll actually get avocado oil, and I’ll put a mixture of olive, avocado oil, and MCT oil in a salad dressing and use that, and usually some kind of protein, beef, chicken, fish, a lot of fish. I used to eat a lot more beef and chicken in the past, but now about 50% of my dinner would be some type of fish usually with a green vegetable. That could be asparagus – I love asparagus – broccoli, cauliflower. Mashed potatoes is probably a big staple of mine because you make the mashed potatoes. You can add a lot of butter to it and even a little bit of MCT. That becomes a really – or coconut oil. That becomes a pretty good staple of mine.

It varies, but I generally keep the ketogenic ratios even if I’m at home or if I’m traveling. People use the excuse of, “Well, I can’t do the diet just because I’m travel too much.”

Dr. Pompa:
As much as we travel at all. I just –

Dom:
Yeah. It makes it easier, actually. I think it makes it a lot easier because you know what you’re going to eat.

Dr. Pompa:
What do you like about the powdered MCT versus the liquid? We ask because maybe we should carry it here. We have a liquid here.

Meredith:
We have a nice liquid, but – yeah.

Dom:
Yeah. I like the liquid, too. If I just take the liquid on an empty stomach, my tolerability is about one and a half tablespoons, maybe two tablespoons on an empty stomach.

Dr. Pompa:
Me, too.

Dom:
If I add it to food, it’s a little bit better. About a year or so ago, I was kind of working with Quest Nutrition just kind of as a – just helping them. I want them to develop a ketogenic meal line. They were developing a medium chain triglycerides. They spray-coat the triglyceride with a probiotic soluble fiber. Quest MCT oil powder is out there. I tested it and realized that it allows a person to take more MCT. I think I could tolerate up to 12 to 15 scoops per day.

Dr. Pompa:
Wow!

Dom:
I could literally keep my ketones at about 1.5 to 2 millimolar per day above what I normally do. The powder, when you ingest it, the soluble fiber tends to slow gastric absorption a little bit. A lot of the issues people have with MCTs is that is just kind of goes through you so fast. When it’s spray-dried with this soluble powder, then – and there will probably be other versions of powdered MCTs coming out that are formulated in different ways. I find that I don’t have the GI issues, especially on an empty stomach. Since I can tolerate more, I can get my ketone levels up a little higher.

Dr. Pompa:
That’s a problem I have. If I do even two tablespoons, I’m bloated out, running to the can.

Dom:
For traveling, too, it’s much easier to travel with a powder than with a liquid. If I’m traveling overseas, I can just take a little Zip Loc bag, and pour in some scoops of MCTs and bring it with me. It’s not looked at suspiciously when you go through security. It’s a practical – and it tastes really good. If you just add it to coffee, it takes like coffee creamer.

I find this to be really versatile. I think most –

Dr. Pompa:
Okay. Got it.

Dom:
I kind of helped beta test this. I was at Nutrition Smart, and I saw it. It’s already on the shelf, already. You can get powdered coconut oil and powdered MCT oil.

Meredith:
Powdered coconut oil.

Dom:
There’s absolutely no artificial sweeteners, or no fillers, or anything in there. I think they use a little bit of calcium caseinate just to coat it, but it’s no protein amount. They use a soluble fiber to spray-coat it. Yeah, it’s really tasty and palatable. That’s kind of my choice.

There’s another product on the market, KetoCaNa. It’s made by KetoSports. It’s a sodium and potassium beta-Hydroxybutyrate powder. One could just combine the MCT powder with the beta-Hydroxybutyrate salt together. This is kind of what I do in the afternoon. If I’m needing an extra kick, I’ll do a scoop of each.

Dr. Pompa:
You do that in the afternoon a lot?

Dom:
I do, not all the time, but I do. Especially if I’m at my desk and I’m – have long days ahead of me, like midday, I’ll boost my ketones. I’m usually sitting at about 1.2 to 1.5 millimolar in the day. If I take a little bit of that, it shoots me up to 2.5 and up to 3. I feel like I can really hammer out and really focus on some work.

Dr. Pompa:
That was the question we had for you. What’s your favorite exogenous ketone? She just sent me – well, had someone send me the one you just mentioned.

Meredith:
Sample of the KetoCaNa, which is the salt, you said, just to clarify for our viewers?

Dom:
Is what?

Meredith:
It’s a ketone salt?

Dom:
Yes. It’s beta-Hydroxybutyrate with sodium and calcium.

Dr. Pompa:
Is that the one you like?

Dom:
I like it, yeah. It tastes pretty good.

Dr. Pompa:
There’s a lot on the market. There’s a few multi-level ones, which –

Dom:
Yeah. There’s some other ones, and they kind of claim to use the thing – the product that we used in the lab. To their credit, they are using a formula. The formula that we tested in the lab was MCT combined with beta-Hydroxybutyrate salts. That combination gives a better pharmacokinetic profile. It’s better tolerated, and we see enhanced therapeutic effects when that combination of the MCTs and beta-Hydroxybutyrate are used together.

Pruvit is out there. They sell a product, Keto-OS, which is pretty good. I like that product, and the KetoCaNa products. There’s also a company out there, actually, the stuff I’ve been testing recently, and I really like it. It’s called Kegenix. Kegenix is new. I think they kind of stay a little bit low profile, but it’s a quad salt, which means there’s sodium, potassium, calcium, and magnesium beta-Hydroxybutyrate combined with a powdered MCT product. I have some bags around here somewhere in my suitcase. I’ve been testing that.

What I do during the day when I’m fasted up to about 2:00 in the afternoon, I’ll check my ketones, and I’ll take the product. I’ve been testing different – I usually test a product five times. I’ll get five curves of my glucose and ketones every time. I really like the Kegenix products. It’s a little bit, maybe, watered down, so it could be – I think they’re going to make a product that’s more geared toward the medical community, but the Kegenix MCT ketone salt product is one that I’ve been testing, and I really like it. It’s on the market now.

Dr. Pompa:
KetoCaNa, you like. You like Kegenix.

Dom:
The Pruvit product’s pretty good, too. I like that.

Dr. Pompa:
Yeah, the Pruvit. One of the things that I’ve seen with some of the advertising – I don’t know if it’s Pruvit or one of them, but it’s almost like they’re saying, “Hey, this will put you in ketosis faster.” Not really. It really just puts ketones in your blood. That doesn’t mean you’re in ketosis. Would you agree with that?

Dom:
Yeah. I think the marketing is definitely over the top. It’s not something that I approve of. I’m not associated with any of these companies.

Dr. Pompa:
I know.

 Dom:
I don’t have ownership. I’m not a spokesperson for any of these products. What we do, our university will create some intellectual property behind specific types of ketones and their combinations. Some of the companies have gotten license for that with the stipulations that they have to use this specific kind of ketone in this specific combination. If they’re using things outside of – if they’re using a different kind of ketone salt or a different formula, then they’re not going to be getting the beneficial effects of the ketones that we see. We spend a lot of time and effort identifying what ketones would be most therapeutic and most efficacious. A lot of that time and effort was a lot of money to really nail down the ideal formulas.

I think that these guys coming out with products, I think it’s a good – in no way will they be anywhere near as potent as the ketone esters. The esters will be incredibly ketogenic, and they will be in the realm of the special operations community and also as medical foods. I’m working with a company that they think they might be able to bring this to market to the general population, too. It’ll be sort of like these products times two eventually on the market, but they don’t taste good.

The more potent a ketone product is, the palatability is inversely proportional to the potency. The more potent these ketone esters are, the more unpalatable they become. We’re working on the palatability issue. I think that’ll be solved in about – within six months, and there’ll be a product on the market that’s very potent.

Dr. Pompa:
I’d be interested in talking to you about doing just a physician line of the keto ester products, just a physician line, not over the counter prescription, but a physician line of products. We carry mostly physician line supplementation. It can only be bought through physicians, and maybe that’s a way to go with that product.

Dom:
Yeah. Yeah. We’re doing a lot of the safety studies right now. The idea is to, within the near future, to get generally recognized as safe, is what’s called GRAS, get GRAS approval for the product. All the data is there, and we’ve done chronic, 15-week, very high dose feeding studies, where we look at liver function, kidney function, every possible biomarker. We know that this is safe. It’s putting this together as a package and just showing it to the FDA that these break down to bio-identical ketone molecules when they’re ingested.

You break the ester bond with intracellular esterases, and it liberates the ketone. Whatever is esterified to use, usually something found in nature, can go to the liver. That also gets broken down into energy metabolites and even ketones. That’s what we’ve been putting together different types of esters.

The main application right now, though, is for these genetic disorders and the special ops community, but I think a sort of less potent or mid-range, somewhere between the ketone salt products and somewhere between the special ops community product, somewhere in the middle. It won’t be dangerously potent, but it’ll be something that would really be of interest to elite level athletes, I think, and also for a physician – what you mentioned, a physician-based medical line, I think, would be important.

Dr. Pompa:
Yeah. Right. Yeah. I think you motivated me to – when I’m in ketosis, I’ll just use some exogenous ketones as that boost kind of like you do, lacking sleep or time, just use it as a boost. Otherwise, my body is producing it by itself for the breakdown of fat, which is important. I think I’m going to start utilizing it more as we’ve been experimenting with it. These people that are trying to break into ketosis – I was worried that it might slow it down, that they may not keto-adapt if they’re taking exogenous ketones. You’re saying that that’s not the case, that it would help with the symptoms but not stop them from breaking into ketosis. True?

Dom:
Yeah. I think it can mitigate the symptoms and also maybe stimulate those ketolytic pathways, so stimulate the metabolic pathways that are important for using ketones for fuel, for shuttling ketones.

Dr. Pompa:
Yeah. It might help.

Dom:
If the ketones are there in the system, the body will actually upregulate the transporters for that.

Meredith:
Makes sense.

Dom:
If you have people – patients that are Type 2 diabetic, what we find – we have a paper under review now – I think it just got accepted – showing that when you give an exogenous ketone, it lowers blood glucose. We don’t actually know how it’s working, but I can tell you from – we do a lot of metformin studies for our cancer research. I could say pretty convincingly that exogenous ketones have a much greater effect at lowering blood glucose than a diabetic drug like metformin. It’s really potent. I think this could be a pretty effective way to manage Type 2 diabetes.

Dr. Pompa:
Yeah, yeah.

Meredith:
It’s quite exciting.

Dom:
It’s a big population of people.

Dr. Pompa:
They have trouble fasting, right, more so than the average person.

Dom:
Yeah.

Dr. Pompa:
Utilizing ketones would make even a fast, which has all types of different benefits even than ketosis, utilize that. Seyfried always says, “Glucose down; ketones up. Ketones up; glucose down.”

Dom:
Yeah.

Dr. Pompa:
How that happens, obviously, the body regulates – they work opposite. I can see this being utilized. We love fasting, people, intermittently, long, four-day fasts, 10-day fasts, whether it’s beef stock, whey water, or just water. This could really make a diabetic break into fasting a lot easier if they have that little bit of fuel.

Dom:
Yeah. That’s great that you do that because I think not only are you deriving a lot of physiological benefits by enhancing metabolic physiology with the fast, but you’re also training the patient to not be psychologically dependent upon food.

Dr. Pompa:
Yeah.

Dom:
I’ve talked to a lot of people who fast, and many of them – some of them had what I would call a preoccupation with food. They’re obsessed with eating. By doing intermittent fasting or just occasionally doing fasts, they feel like it puts them in control of the food. Initially, they might get some crazy cravings, but after they do it for a while, they feel like they have so much more psychological control over their appetite.

Their appetite becomes regulated because their metabolic physiology improves. It has a double effect by improving their overall psychology behind food, itself.

Dr. Pompa:
Dr. Dom, you should see the benefits. We teach people to even do a four-day fast once a month, every other month. Every fast, we see a different level of healing because just what happens. I don’t even think we understand from a scientific point, these amazing things that transform metabolically throughout the body. At the cellular level, every fast heals. Periodic fasting just reconditions the body, like I said. That’s how you get them eventually becoming efficient at utilizing fat and ketones. Remarkable things happen during fasts.

Dom:
Yeah. I think that’s definitely the case with almost everybody. I think you got to gauge the fast a little different. I’m sure there’s an art and science to how you do this. When it comes to some of the patients that contact me, some of them have – are cancer patients that have gone through chemo. The standard of care had failed, and they want to know what options. If they have a healthy or a high BMI, they are ideal candidates for a fast. They’ve been told to drink as much Ensure and sugary things as possible.

You get the patient that has – chemotherapy is incredibly catabolic and contributes to cachexia. Sometimes you get patients that are kind of wasted, and they really need to build themselves up. Sometimes fasting is not the best situation for them, but a ketogenic diet that’s well formulated could actually add muscle if they do some strength training on top of that.

We completed a study. It’s under review, hopefully published soon – that an elite level advanced athletes showing that you can actually add lean body mass study with a ketogenic diet.

You can lay down new muscle on a ketogenic diet.

Dr. Pompa:
When I go into ketosis, I actually gain muscle because I spare my muscle, honestly. My body just kind of eats muscle too easy, especially if I’m doing endurance sports. When I’m in ketosis, I spare my muscle when I’m doing endurance sports, and I actually can put muscle on. It really benefits me that way.

That’s why we use whey water fasting oftentimes for those people. We use beef stock fasting, so we utilized it. Of course, we use ketosis and fasting. We utilize these things in different tools. Ultimately, the restriction – Seyfried’s right. Restriction plays a role. Again, it’s not purposely, necessarily caloric restricting diets. We get people to the point where they automatically start eating less, but we do it through a lot of these temporary restricted moments, whether it is ketosis, whether it is a fast, whether it is daily intermittent fasting. It works. It’s just amazing that it happens.

Meredith:
Many people fear losing muscle mass when they get into ketosis or, you had suggested, a ketogenic diet, but that’s not usually the case.

Dr. Pompa:
No. Not necessarily true.

Dom:
No. Each person, you got to adjust the calories and the level of protein, but no, that’s not the case. You can gain muscle. I’m a big proponent of resistance training, too.

I think if you couple the ketogenic diet, you could further enhance the muscle-building effects with resistance training [01:11:20]

Dr. Pompa:
My son went – he put on massive muscle like that when he went into ketosis. He kept his protein up and his caloric intake probably more so than the average person looking to lose weight, but it worked for him. He gained all this muscle and got lean.

Meredith:
How old is he?

Dr. Pompa:
Seventeen years old.

Meredith:
Seventeen.

Dr. Pompa:
He got ripped and lean and put on muscle. It’s amazing to watch. We’re at the end of our time. I’m telling you, we could probably do a three-hour show.

Meredith:
We’re done. I know.

Dr. Pompa:
This is a topic that we love.

Meredith:
Near and dear.

Dom:
I can tell. Yeah. That’s great.

Dr. Pompa:
Yeah, exactly. We could go on – matter of fact, make us a promise you’re going to come on again because we –

Dom:
I would love to. Yeah – would love to.

Dr. Pompa:
Great.

Dom:
I’m sure there will be more questions, too, as –

Dr. Pompa:
Yeah. Fire away. I would love to even have you – gosh, maybe we should get him in April seminar, Stephen Phinney and you, Dominic.

Meredith:
That’d be great.

Dom:
I would love that.

Dr. Pompa:
We’ll see if your schedule’s clear. This would be –

Dom:
Okay.

Dr. Pompa:
There’s just so much to learn. Look, this is an important tool, really, that I believe is part of an answer to an epidemic of problems and why people don’t feel well, hormone, neurological conditions, neurodegenerative conditions, just fatigue, everything that people are – brain fog, all of these conditions. What we’re talking about is part of the answer. That’s why we want to get this message out.

Dom:
Yeah – and to get it mainstream. I’m at a medical college, so our medical school has a few hundred medical students. I’m giving a lecture on all this in about three weeks. The enthusiasm from the medical students, they’re like, “We don’t get” – first of all, they’re not taught any nutrition. This is something that’s completely foreign to them. I’ll give a little lecture on it or mention it in a lecture, even though it’s not part of what they should be learning because it’s not part of the medical boards. The school kind of dictates what’s on the curriculum based on what’s on the boards because they want the scores to be good.

From the standpoint of the student interest, they have more interest in this than most topics that they’re covering. I get a lot of interest from medical students saying, “I want to incorporate this into my practice. We’re not even taught this information. It is so important. It could literally put Type 2 diabetic into remission, and we’re not – we’re just taught to write a prescription and not tell them to change.”

They say, “How should we lower a diabetic’s blood glucose?” “Well, with more insulin. That’s how you lower a diabetic’s glucose.” They’re not taught to use food as medicine. I think that needs to get mainstream. What we’re talking about is really a powerful metabolic therapy. It’s not a fad diet.

Dr. Pompa:
No.

Meredith:
No.

 Dom:
That message needs to get out.

Dr. Pompa:
No. This is a tool that we’ve seen work for so many different things and just transform so many lives. Really, it’s part of who we are as humans. Every culture that’s lived long and healthy, ketosis is a part of it.

Meredith:
Amen.

Dom:
Yep.

Dr. Pompa:
Yeah, no doubt about it. Gosh, we will have to do a part two.

Meredith:
Yes. We have to do a part two.

Dom:
Okay. Thank you.

Meredith:
Thank you so much, Dom, for your amazing research and what you’re doing to get this information out to the public. Any final words?

Dom:
I just want to thank you guys, like I said, for getting this information out there. I could spend all my time in the lab, but if it’s not for people like you that recognize that this research has tremendous benefits for the end user, the patients, I think I’m just very thankful for that, that you kind of acknowledge the research that we’re doing. I’m working on a more comprehensive website, but I do have a website where I’ve compiled information.

Dr. Pompa:
Give us that website right now.

Dom:
KetoNutrition.O-R-G. I’m working on another one, maybe even a podcast and a more extensive blog in the future. That’s sort of in the pipeline, something that I’m working on. I would like to get – we could talk offline – a list of the doctors. I would like to add the doctors that are ketogenic savvy, nutritionists that are keto savvy, I guess, so I can put it on that website as a list of resources for patients to go to.

Dr. Pompa:
Absolutely. We have doctors trained around the country in this. You had said you really have to work, those watching, with someone who is trained because electrolyte depletion – there’s a lot of things that people do wrong.

Dom:
Absolutely. Yup.

Dr. Pompa:
Lose muscle, get sick, rapid heart rate, drop of energy, we see it all, and it’s common mistakes that are made. Absolutely, you want to work with a practitioner who understands ketoadaptation, for sure. We’ll give you that list, Doc.

Dom:
Okay, great.

Dr. Pompa:
We’re training doctors around the country that understand these principles, the fasting, and ketosis, and cellular healing, and detox. That’s what we do. Thank you. KetoNutrition.org –

Dom:
Yeah.

Dr. Pompa:
We will absolutely send people there, and we’ll give you the practitioners for there. We’re going to do a part two, Dom. Thank you so much.

Dom:
Thanks for having me. Appreciate it.

Dr. Pompa:
Absolutely.

Meredith:
Thanks, Dom. If you’re watching and want to know more about the ketogenic diet, head over to Dr. Pompa’s website, D-R-P-O-M-P-A dot com. Two articles on ketosis, one laying out the framework and then another on troubleshooting. If you’re kind of wondering about Dr. Thomas Seyfried, who we mentioned, as well, we did an episode with him. It was, I believe, episode number 95 on Dr. Pompa’s YouTube channel. You can check that out, as well.

Dom:
Okay. Okay, great. Thank you. I’ll check it out.

Meredith:
Dom, thank you. Thanks, everyone, for watching. We will see you next week. We’re going to be interviewing Robby Bessner on EMFs, electromagnetic fields and learning a lot more about that and some of the health issues surrounding those. Tune in next week for Episode 99. We’ll see you next time. Thanks for watching.

Dr. Pompa:
Thanks, Dr. Dom.