Dom D’Agostino Ketogenic Diets : Exogenous Fat-Burning Ketones

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Guest Bio – Dr. Dominic D’Agostino

Dr. Dominic D’Agostino is an Associate Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine. He is also a Visiting Senior Research Scientist at the Institute for Human and Machine Cognition (IHMC). His laboratory develops and tests metabolic-based strategies for targeting CNS oxygen toxicity (seizures), epilepsy, neurodegenerative diseases, brain cancer and metastatic cancer. The approach to utilizing metabolic-based strategies can be applied to a wide variety of pathologies linked to metabolic dysregulation. His research is supported by the Office of Naval Research (ONR), Department of Defense (DoD), private organizations and foundations.

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Global interest in ketogenic dieting, exogenous ketones and the effects of ketosis continues to grow exponentially, with new pathways and discoveries showing that it benefits people looking to boost energy, control appetite, and live healthier lives, as well as people who struggle with metabolic disorders. Dr. Dominic D’Agostino broke down the benefits of the ketogenic diet and the effects of ketosis on fat metabolism and fat loss. How does the diet aid in fat burning? “When you stop eating, you essentially start to liberate your body fat stores. You liberate fatty acids from your fat stores called adipose. These fatty acids are actually the preferred fuel for your body.” Putting ketosis in an evolutionary context, it was a natural state to be in due to food availability. Hunting males had to be in survival mode but still needed the energy to track and kill animals. It was necessary to thrive in the fasted state – anything else threatened survival. Their way of eating was a lot like intermittent fasting, but this one was more of a result of circumstance not choice.

Dom also shared his background and how he took an interest in ketogenic dieting and ketogenic eating plans. He studied how to prevent the oxygen toxicity seizures that occur in Navy Seal divers that use closed circuit rebreathers. “The data was pointing to preserving brain energy metabolism, because high oxygen can start to disrupt brain energy metabolism. It’s a stimulant at high levels and it can contribute to free radicals, what we call reactive oxygen species. The ketones would essentially make the brain function so efficiently that it wouldn’t be spitting out these free radicals.”

Dom also gave more detail about the ketogenic diet and how it impacts the body’s fat burning process. The diet is “90% fat, it mimics the metabolic physiology that you have in a fasted state. It puts a lot of fats into your bloodstream and your body thinks it’s burning its own fat stores because there’s an absence of carbohydrates.” He went onto share his expertise on applying the diet into daily life. There are two ways to approach the ketogenic diet, strict or modified. In modified, the protein is more liberal (20-30%) and carbohydrates would come from high amounts of green, leafy vegetables like cauliflower, kale, spinach, asparagus, broccoli, cauliflower and all sorts of salads. Fat would come from macadamia nuts, avocado, olive oil and nuts. In a strict ketogenic diet, these foods would be limited. Your diet would be filled with proteins like fatty cuts of meat, chicken with the skin on it, a rib eye steak instead of a lean steak, fatty cuts of pork, bacon, as well as eggs.

How can a ketogenic dieter get the most out of the practice? One way to apply it is by doing intermittent fasting then eating your ketogenic diet food within a 6-hour window. You can take the ketone supplements within that eating window, and also have them during the fasting state to further enhance the benefits of fasting. In doing so, it essentially enhances your metabolism to burn more fat. Dom went on to recommend the best exogenous ketone brands, Kegenix, Pruvit (Keto OS), Ketopia and KetoCaNa.”

We also discussed how people can detect whether they are in ketosis. “If we go to the extreme, to the epilepsy patient or the person who has a metabolic disorder, it could be as high as 3 to 4 millimolar. For the normal person that’s just using it to enhance their energy levels, cognitive state or their physical well-being, I would say anywhere between 0.5 to 2 millimolar would be the ideal level to be at.”

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Orest: This is Orest, the Old Guy from today talking with Dr. Dom D’Agostino and I am privileged. I do, I mean privileged to be speaking with Dom today. Dom is a assistant professor at the University of South Florida College of Medicine, Department of Molecular Microbiology and Physiology, and that is a mouthful to say. Dom is a leading expert on ketogenic diets and exogenous ketones. By exogenous, I mean that you can go to your Amazon account, order them, and have them delivered to your door the next day if you have a Prime Account. That’s what exogenous means. Dom’s Been on the TED Talk. He’s been on Tim Ferriss’ podcast and has been on numerous scientific and popular programs.

Now, this part is to make my lawyer happy. Do not do this on your own. Work with an experienced, and we’ll probably talk about the word experienced, healthcare professional. Any products that we’ll mentioned, I’m going to have a link to them below that we’re going to talk about in the product. That’s pretty much what we’re going to have. For you listeners here, I watched Dom and Rhonda Patrick, she’s another very smart person, discuss ketogenic diets a few weeks ago. Actually, I watched them just a few months ago and then again just recently. They really got into the weeds. Sometimes when I was listening to them, it sounded like Klingon with the vocabulary they were using, the 2 scientist talking at a very high level.

Today, I want to break it down. We’re going to break it down for the non-scientist, the person who has no knowledge of ketogenic diets or very little knowledge of ketogenic diets. I’m going to start off with a 2-part question, Dom. I want to talk about what are ketogenic diets, what are ketones? We’re going to focus mostly on talking about fat metabolism, fat loss, and exogenous ketones later on in our discussion today. I want to also give us an overview about in what areas are ketones used to help people in various diseases and things like that.

Dom: Sure. Good question. Before I begin, I just want to clarify my department. It’s the Department of Molecular Pharmacology and Physiology.

Orest: Okay, I guess I was wrong [crosstalk 00:02:59].

Dom: Very close. I bring that up because pharmacology is what I’m supposed to be studying, but we found that nutrition is actually more powerful for what I was studying which was seizures and that set me on the path of looking at the ketogenic diet. Answering your question, I like to begin talking about the ketogenic diet and exogenous ketones from the perspective or the context of fasting. Most people have gone without food for a period of time and for many of them, it’s uncomfortable but I could tell you that after the second or third day, it gets considerably easier because your ketone levels begin to be elevated.

I’ll take another step back. We talk about when you stop eating, you essentially start to liberate your body fat stores. You liberate fatty acids from your fat stores called adipose. These fatty acids are actually the preferred fuel for your body. Your heart runs more efficiently off fatty acids than glucose, for example, and our body runs extremely efficient off of fat. The problem, I guess, you could call it a problem is that the brain cannot transport these fatty acids across the blood-brain barrier.

What our bodies do usually after 24 hours going into the second or third day is that the fat burning process in the body is so accelerated if you stop eating for a couple days is that the fat-burning process in the liver starts to create these ketone bodies which could be thought off as water-soluble fat molecules. Fat molecules range in size from 8 carbons to 20 carbons and think of your liver as a wood chipper, and it chips them up into small little molecules that are now can cross membranes. Once these ketone bodies which include something acetoacetate or beta-hydroxybutyrate, once they get into the bloodstream, then they can essentially replace glucose as the primary fuel for brain energy metabolism.

There was work done years ago showing that when you burn ketones for energy, it’s like burning a high-octane fuel. We come up to the gas pump and we have regular and we have high-octane. The ketones would be the high-octane fuel. From an evolutionary context, if you’re a male and you’re out there hunting 10,000 years ago in the absence of food, if you didn’t have energy, if you didn’t have your wits about you, if you weren’t thinking lucid, then you couldn’t seek, track down, and run down the animal. The people that did not thrive in a fasted state probably failed to procreate and adapt to the environment and move on.

Being in a state of ketosis is more or less a hardwired evolutionary adaptation. It’s due to not only the food selection we had thousands of years ago, but food availability. You could argue that being in a state of ketosis is actually a natural state to go in and out of ketosis from periods of time. Obviously, human population would stumble upon fruit trees and would gorge themselves or kill an animal and would gorge themselves. It was more like intermittent fasting but on a survival stage, if you will. It’s not an unnatural state.

Modern medicine considers being in ketosis an unnatural state because it’s associated with type 1 diabetes and that’s called diabetic ketoacidosis. That’s very different from what I’ll be talking about which is nutritional ketosis. In a fasted state, it takes you about 2 to 3 days for your body to start producing these ketone bodies and then your brain can shift from using glucose to using ketones as an energy source. That can be beneficial in many ways but it’s very difficult to get to. One way to mimic the fasting ketosis is to follow a ketogenic diet.

Ketogenic diet is the classically used ketogenic diet at Johns Hopkins. It’s 90% fat. When you’re eating it, it more or less mimics the metabolic physiology that you have in a fasted state. It puts a lot of fats into your bloodstream and your body thinks it’s burning it’s own fat stores because there’s an absence of carbohydrates. It essentially senses that you’re not eating and it starts to … The accelerated fat burning process starts to make these ketone bodies. Even with the level of calories that you can maintain your weight, you can produce a state of nutritional ketosis. This has been the standard of care for drug-resistant epilepsy since the 1920s and 1930s until anti-epileptic drugs hit the scene in the ’60s and ’70s.

It had a resurgence in utility back in the mid 1990s with Hollywood producer Jim Abrahams gave a story in Dateline NBC about his son Charlie. His story was that they tried every anti-epileptic drug under the sun in combinations and nothing worked until they used the ketogenic diet. He was not told by his neurologist that the ketogenic diet was an option. It probably did a lot of damage along the way with all the drugs and when he used it, it worked remarkably well and the scientific literature supported this as being an underutilized, highly effective therapy. He wanted to gain more publicity for it and he started the Charlie Foundation.

Meryl Streep was his friend, a Hollywood producer so he’s rubbing elbows with different Hollywood celebrities. Meryl Streep did a movie about the ketogenic diet and it’s called First Do No Harm. I watched that movie back in 2008 or 9 and it really motivated me to study the ketogenic diet, to study fasting ketosis. With my military contracts, I became interested in leveraging the power of ketones into a substance, into what we call exogenous ketones, so found outside the body. Something that could be consumed in a shake, in a pill that can put you, that can elevate your blood ketone levels and start feeding your brain the super fuel. I realized that there was tremendous applications.

I’m actually surprised that nobody was studying this. I shouldn’t say nobody. Actually, the NIH was studying this and Oxford University was studying this and this was … I found this out throughout a series of patents that had been filed and also there was a number of grants that had been awarded by DARPA for what was called Warfighter Performance Enhancement.

Orest: What’s DARPA?

Dom: DARPA is a … It’s a secret organization. It’s a defense organization that does a lot of top secret things. You’d probably see them mostly in the robotics industry. They’ve advanced that considerably, drones, but they also dabble in physiological, biological, scientific development, tech transfer and development. A lot of military-based applications, and I could say a lot of the stuff that the military is using evolves from DARPA related projects.

DARPA had been funding and the Department of Defense had been funding some research. That caught my attention and I pitched the idea to my program officer at the Office of Navy Research because I was studying oxygen toxicity seizures which occur in Navy Seal divers that use a closed circuit rebreather. It allows you to go scuba diving but you don’t have any bubbles, so there’s a stealth component to it. It allows you to evade your enemies so you could sneak up on them in a quiet lake in the middle of nowhere. The disadvantage of that type of equipment is that if you dive down too deep, the high concentration of oxygen can give you a seizure.

I was studying why these seizures occur and how to mitigate it, how to prevent them from happening. All the data was pointing to preserving brain energy metabolism because high oxygen can start to disrupt brain energy metabolism. It’s a stimulant at high levels and it can contribute to free radicals, what we call reactive oxygen species. The ketones would essentially make the brain function so efficiently that it wouldn’t be spitting out these free radicals, kind of like an engine running off really clean high octane fuel does not spit out as much carbon. It burns more clean. Essentially, that’s what’s happening when your body and brain is running off ketones, is that the oxidation of the ketone molecule does not liberate or spit out, if you will, as much free radicals. You have a cleaner burning fuel.

I recognize this from a scientific theoretical point of view but then the next step was to determine what types of ketone molecules we could develop and also which ones were most effective for the different types of applications that we’re interested in applying them for. Now, it started with oxygen toxicity seizures but now we study about a dozen or more different applications for exogenous ketones. It would also work, the ketogenic diet is one way to get yourself into ketosis and you could do therapeutic fasting, the ketogenic diet, or ketone supplementation. You could do a combination of that. You could do intermittent fasting which is basically not eating all day and then eating within a 6-hour or so window. Then you eat your ketogenic diet food during that time and then perhaps maybe some ketone supplements. Then maybe even have ketone supplements during the fasting state because it would further enhance the fasting, the benefits of fasting.

These are some of the protocols that we’re interested in developing and applying to managing cancer to managing seizures and also to warfighter performance because if you’re a special ops guy out in the field, you don’t have a lot of time to eat. You have limited food availability. Something that would make you more resilient to an absence of food and keep you cognitively and physically resilient are all things that the military is interested in. These are things that we are urged in studying, keeping that cognitive resilience under extreme environments of altitude, of hyperbaric environments. That’s a little snapshot of what ketosis is and the ketogenic diet and exogenous ketones. Now, there’s just so many different applications we’re studying.

Orest: Sure, sure. Well, that’s actually very interesting stuff and I think the military applications and the performance applications are really useful. Could you go into a little bit about how in the ketogenic diet, how fat is used as an energy source?

Dom: Yeah. A lot of the benefits of the ketogenic diet is that it really forces your body to liberate fat stores, to liberate the fatty acids, I should say, from fat stores. In doing so, it essentially enhances your metabolism to burn more fat. This has been shown experimentally in various studies that have been done. The one that comes to mind is Jeff Volek’s study at Ohio State University conducted at University of Connecticut. He’s at Ohio State now. He had elite level athletes that were adapted to a high-carbohydrate sugar-burning diet and that were performing in a very high level and athletes that were performing at a similar level but had been following a low-carb, high-fat ketogenic diet.

If you look at O2 consumption and CO2 production, the respiratory quotient, you can determine what the body is using for fuel. He was able to show very convincingly that if you’re adapted to a ketogenic diet that you’re burning about at least 2 times the amount of fuel, of fat for energy. The athletes had actually changed their metabolic physiology to use fat as an energy source. That has tremendous advantages because in the context of an ultramarathon, if you have 2 guys, one carb adapted or sugar burning and one fat burning and they start running, your sugar stores in the form of glycogen will run out after about 1,500 to 2,000 calories, your stores in your muscle and your liver.

If you’re pulling off your fat storage for energy, your sparing your glycogen in the liver and the muscles because you’re preferentially using the fatty acids for fuel. Even a lean person has 30,000, 20 to 30,000 calories of fat for energy stored on their body because fat is very, very energy dense. It’s got 9 calories per gram. Even if you pinch the skin on your forearm which is very thin, it’s still a lot of fat because it’s surrounding, encapsulating your whole body. Then in your lower back, beneath your butt, and your thighs, you have lots of fat on your body. Even in a lean person or person that looks lean. From a practical standpoint, that’s pretty huge.

Being fat adapted has a tremendous advantage as far as substrate utilization, as far as extending your performance. That has implications for the old guy, the guy that’s trying to lose fat. If he restricts his carbohydrates, it’s naturally forcing your body to burn more fat for energy. With carbohydrate restriction and adding more fat to your diet, that has a satiating effect on your brain. It’s telling your brain it’s not as hungry because you don’t have the blood glucose fluctuations. There you have a practical maybe perspective of the diet.

Orest: I understand, and I don’t know if this is accurate, I just heard this that Lebron James went to South Africa to work with someone on getting on the ketogenic diet. Are you familiar with that?

Dom: Yeah. I know it. Probably Tim Noakes maybe would be. Tim Noakes is a doctor, a physiologist that advanced this idea of what’s called the central governor theory that in exercise performance, the fuel flow to your brain will dictate the extent of your performance and perceived exertion, reaction time, motor recruitment. If your brain is getting lots of energy in the form of ketones which will be high even if you’re in a fasted state and even if you’ve run out of your stored sugar stores, your body’s burning fats, so you have a steady flow of energy to your brain in the form of ketones. That would preserve your brain’s energy.

That’s extremely important for athletic performance because maintaining and preserving brain homeostasis maintains neurotransmitters. Like I mentioned, there’s perception, your perceived exertion is less. Your reaction time is faster, very important for basketball. Your brain activates your muscles. If your brain is functioning with a high energy fuel, it’s sending signals to your muscles to contract so you’re faster. Your reaction time is better. These all can have tremendous implications for the athlete.

I think one of the nutritionist is Cate Shanahan and we have met a couple times. At least one time, I think we’re in Social Health Symposium and sat next to each other and had a nice chat. She was working with a number of athletes and adapted them more away from a carbohydrate-based diet to a high-fat, low-carb diet that would put the athletes into ketosis and they were performing better and their body composition changes were impressive. Lebron James has been in the media a lot with [crosstalk 00:21:29].

Orest: Yeah, exactly. You touched on this and I want to go into just a little bit more. When you’re on ketosis, what effect does it have on appetite and calorie intake?

Dom: I think that’s a really good question because I think the effect of a ketogenic diet and ketones in particular on appetite contributes to what could be the main benefit of the diet is that it suppresses your appetite. I think suppress is the wrong word. It controls your appetite so your appetite is not controlling you. If you’re on a high-sugar diet and I remember being on one 10 years ago, and it doesn’t have to be sugar. It could be eating fish and rice. Two or 3 hours later, I was getting hunger pangs. I was getting cravings for some, for bread, for carbohydrates, for a candy bar or something.

When you’re on a high-fat ketogenic diet, your blood glucose is very stable, your insulin levels are very stable. You don’t have what’s called the postprandial hypoglycemic dip. After we eat, our insulin gets released from our pancreas. It’s stimulated by the glucose that enters our bloodstream. That insulin in some people, what happens is that the insulin disposes off a lot of glucose and you get a hypoglycemic dip. Your blood sugar becomes low after you’ve eaten a lot of sugar and that makes you crave sugar more. You want to repeat that and do it over and over. It’s vicious cycle. That’s completely abolished or significantly attenuated if you’re on a ketogenic diet.

You can look at people who wear a continuous blood monitor called the Dexcom. I have a student that’s type 1 diabetic that had shifted from a carbohydrate-based diet to a ketogenic diet. Instead of his numbers going like this all day, his numbers do very little fluctuations all day and his mind is sharper. It’s much safer for him because he doesn’t have very low lows or very high highs. If your glucose is really high, that’s essentially making your blood like sludge and impeding blood flow to your eyes. If you’re type 1 diabetic and your glucose is sky high, you could go blind. You could destroy your kidneys.

I know it’s bit controversial but if a type 1 diabetic was to go on a low-carb, high-fat diet, it would use considerably less insulin to manage. Whenever you’re using less insulin to manage your type 1 diabetes, that’s a good thing. Any doctor who says otherwise is not in his right mind. Doctors are not advocating the use of low-carb ketogenic diets for type 1 diabetes. They’re starting to come out a little bit on board. There’s even a book called the Ketogenic Diet for Type 1 Diabetes by a medical doctor who’s a type 1 diabetic but it’s not embraced because people think eating this way is so hard. I don’t find it hard personally. Most people who give it a chance won’t find it very hard to do.

Orest: Let’s talk a little bit about the ketogenic diet, the modified ketogenic diet, and protein intake since we’re in the subject of eating. What’s your views on that?

Dom: That’s a good question. It’s really important to remember that the ketogenic diet is a medical therapy. It was developed originally at the Mayo Clinic, implemented at Johns Hopkins, and I think there’s about a hundred and fifty to 200 different centers in United States that are linked with the Charlie Foundation actually that have dietitians that implement this. It’s supposed to weigh out your food and it’s very high in fat. In grams, you have … There was a 4 to 1, 3 to 1, 2 to 1. I don’t want to get into discussing all the ratios but essentially, the clinical classic ketogenic diet is about 85 to 90% fat and very low in protein, and people don’t realize that. It’s 8 to 12% protein and then the rest of it being a very small amount of carbohydrates.

What has become popular over the years is the use of the modified ketogenic diet or modified Atkin’s diet it’s also called. That diet is about twice the amount of protein which happens to be about equal to or less than the western diet in protein. It basically becomes an amount of protein that is very comfortable and sufficient for an athlete. It actually fits well into the diet from a practical standpoint if you’re preparing meals. A modified ketogenic diet is about 25% protein, I would say 20 to 30%, 25 with a little bit of wiggle room. About 65% to 70% fat with a balanced maybe 5 upwards to 10% being carbohydrates.

The carbohydrates would come primarily from green vegetables, leafy vegetables, cauliflower. I do a lot of cauliflower mashed potatoes, [crosstalk 00:27:06]. It’s actually a perfect ketogenic food. Kale, spinach, asparagus, broccoli, cauliflower, all sorts of salads. Your fat can come from macadamia nut is a perfect ketogenic food. Avocado, olive oil, nuts. These are all foods that would be incorporated in high amounts in a modified ketogenic diet. Whereas in a strict ketogenic diet, those foods that I mentioned would have to be limited. From a modified ketogenic diet perspective, they’re basically unlimited. Then you would fill in your protein with fatty cuts of meat, chicken with the skin on it, a rib eye steak instead of a lean steak, fatty cuts of pork, bacon, eggs.

Orest: I’m starting to get hungry as you’re talking right now.

Dom: Yeah, yeah.

Orest: One of the things I’ve, because I’ve gotten on this just a little while ago, is using various sauces like Hollandaise sauce, Béarnaise sauce. That’s egg yolks and butter and it makes food taste great. That’s actually [crosstalk 00:28:13] eat on a modified Atkin’s diet.

Dom: I’m glad you bring that up, yeah, because that’s the sauces are things that we were traditionally taught to avoid, the gravy and things like that. They become a perfect way to further boost the ketogenic diet to get your macronutrient ratios into that profile that helps you better maintain ketosis. There’s companies out there making what’s called fat bombs. They’ll make these little cookies or little, I don’t know what you’d call them, like little chocolate desserts, like little chocolate balls actually. They’re made from butter and coconuts and stevia instead of sugar or erythritol. You eat it and it is basically like 90 or 95% fat and it tastes like a desert. Obviously, it’s very filling and satiating because it’s mostly fat. It allows you to get more protein into your meals. If you have these fat bombs during the day, your overall macronutrient ratio would fit in to the ratios needed to keep a nutritional ketosis, and they taste good, too.

These are things over the last decade that ketogenic diet has evolved in ways that allow for compliance, and that’s the big thing. No one’s going to follow a diet if it’s difficult to do. I think it opens up the window for many companies. I know Quest Nutrition launched what was called Quest Keto a few weeks ago. If you go to the website, you could click on … Not only do they have a Reese’s peanut butter cup and chocolate cups, but you can click on Keto Mousse or some beef stroganoff or salmon and then they package it and send it right to your house.

Orest: You have your own mousse that you have talked about.

Dom: Yeah.

Orest: Tell me about your own mousse.

Dom: I like to source out my ingredients whole and make things myself and experiment. There’s different versions of it. Last night, I had 2/3s of it was a coconut cream and I buy Conchita brand coconut milk and I pour off the coconut water and set that aside and use that for other things. Then I take the cream and I put about 6 ounces into a bowl and maybe 1 or 2 tablespoons of sour cream in there, too. It’s basically a bowl of fat and then I’ll add some dark chocolate to it, baking chocolate, and 1 scoop of a plant-based … I’m experimenting now with a plant-based protein source. It’s a protein isolate that’s Dutch chocolate. Then I put a teaspoon of cinnamon and stevia and then about a quarter of a cup of wild blueberries that have almost half the sugar that I source out.

That whole thing has actually a perfect ketogenic ratio. It fits that ketogenic ratio and I can indulge on that every night and it’s the last meal before I go to bed. I see the ketogenic diet as something that’s indulgent because I really enjoy fatty foods. I feel most people that follow the ketogenic diet and are true to it will feel better, will have more energy, and will just have a more stable mood and well-being once they’ve adapted to it. Sometimes it takes, for some people like athletes, athletes actually bounce in and out of ketosis because of long duration athletic events. If they’re a cyclist and they’re on their bike for 6 or 8 hours, they can’t even take up enough sugar and just stay out of ketosis. They adapt very quick. Most athletes adapt very quick.

The elite level athletes that follow a ketogenic diet, for them to get back to baseline and then perform better, it takes them about 3 upwards to 6 months sometimes because you’re change … Well, if you look at the numbers, I think Jeff Volek and Phinney published something years back that showed it took 6 weeks. From a practical standpoint from the athletes that I’ve communicated with, it really takes a little bit longer and it maybe because there’s a learning curve for learning the ketogenic diet. It may take them a couple months to be following a diet that really keeps them into ketosis. If they’re into ketosis, if they look at their numbers, they usually have a dip the first month or 2 and then after about 3 months, they’ve come back to baseline and then they start improving their numbers and their stamina goes off the charts. For elite level performance athletes.

I get a lot of questions. What about the strength athlete? What about the power lifter, the bodybuilder? I think the modified ketogenic diets are actually great for power lifters and bodybuilders especially if they’re trying to lose weight or make a certain weight class. You can maintain your muscle and your strength going into and trying to fit into a certain weight class. I think they’re extremely advantageous. We published an article with our Italian colleagues looking at elite-level gymnasts. Their exercises were lots of dips and chin ups and gymnastic-type exercises. They’re able to increase or maintain their strength on a ketogenic diet and they maintained all their strength and their muscle but they lost more fat when they used the diet to do a body recomposition [inaudible 00:34:11].

Orest: Great, great. Let’s talk a little bit about exogenous ketones. What is the benefit of using exogenous ketones? My experience, I’ve been using exogenous ketones for about a month now, and the first thing I noticed was that I did not get a drop in energy in the afternoon like at 2 or 3:00 which was very common for me. I slept a lot better. I had lot more dreams and also, I wasn’t … My appetite, as you mentioned earlier, my appetite wasn’t controlling me. I actually find myself not avoiding the calories but not wanting the calories as much as I have in the past. Exogenous ketones, I think it’s a really interesting topic for everyone.

Dom: Yeah, yeah. I prefer to run off a combination of endogenous and exogenous but in being a fasted state but only had taken ketones today, so I’m running off exogenous ketones right now and a little bit of my endogenous. What time is it? I’m about 12 hours fasted or whatever, or more than that. The benefits we’re just finding out now, there’s not a whole lot of research on this because there are actually new entities, new molecules. What’s important to recognize is that they are, when you consume them, they’re bioidentical to what your body makes.

Think of it as creatine. You take creatine, your body makes creatine, can derive it from its food sources and can make it but you’re boosting it to super physiological levels. With exogenous ketones, you have the ability to adjust those levels to anywhere. You have a commercially available meter that you can measure and look at your levels and find out where you feel the most energy, where your performance is optimized, and then you can drink your ketones or adjust your diet to get into that ideal optimal zone. That would be great. What if a drug was like that? What if you could take a drug, anti-seizure drug or cancer drug or whatever, and be able to get a commercially available device and say you’re in your optimal range. I think that’s pretty cool that this technology exists for exogenous ketones.

As far as applications, the original application for the first exogenous ketones that were out, well, there were some that were hypothesized or suggested for a wide variety of metabolic disorders. The main application for development and testing of exogenous ketones was warfighter performance, and that’s how I stumbled upon it. I would say athletic performance, there was a study that was published about a month and a half ago by Cox et al in collaboration with NIH and Oxford that showed elite level cyclists had enhanced fat oxidation. They had lower levels of lactate production during exercise, and they had a better time in their trials, in cycling trials.

You have performance applications. The evidence suggest that they were shifting body towards oxidizing fat for fuel even though you are giving exogenous sources of energy of ketones. I think most importantly, the lower levels of lactate that was being produced and it was about 50%, that’s tremendous. If an athlete can keep their lactate levels lower, they have less muscle burn and you can extend athletic performance by suppressing that metabolite which tends to impair muscle contraction. It was lowering that. That came out in cell metabolism which is impact factor of a journal of like 17 or 18 which is pretty significant and it was pretty elegant study. They knew that the work was being done over several years so it is a lot of work.

I actually wrote a review with my colleague Brendan Egan from Dublin, Ireland that was published in the same journal. Just this week, it came out. The title of that article, it’s called Fueling Performance: Ketones Enter the Mix. It’s a couple-page article and it talks about that study, but it also talks about the effects on athletic performance maybe due to the effects of ketones on the brain. By enhancing your brain, if your brain’s happy and energized, it can send signals to your muscle to contract faster with reaction times that are quicker.

You get more motor units being contracted if your neurons are firing faster. Your perceived exertion is less because you’re blocking some of the pathways. If your blood glucose is low, it’s causing fatigue and we call that essential fatigue. A lot of overtraining is really not necessarily the muscles but your central nervous system’s ability to contract the muscles. This is more or less essential governor theory. I think there’s a lot of merit to that theory and we want to test this experimentally with the use of ketones.

I think what’s also important is to look at, to do what’s called metabolomic studies. We’re doing this in animals where we feed ketones and we rapidly decapitate the animal at the end of the experiment and we take the brain tissue and we look at all the different energy metabolites. It showed that the brain has essentially more neurotransmitters associated with sending signals to the muscle and also greater levels of metabolites that are called the Kreb’s cycle metabolites. This is the bioenergetic reserves of the brain. The brain has this higher energy reserves and it has more neurotransmitters, and that can be extrapolated to improve performance.

That would be the first application and the second application would be really what the ketogenic diet, the standard of care, what it’s used for is epilepsy. I’m really excited about this because this could change the whole … It could be a paradigm shift in treating seizure disorders and epilepsy. The ketogenic diet has been underutilized because it’s so hard to implement. A guy could go to a doctor and he gives you a pill, and that’s easy to do. Actually, patients have a hard time just taking a pill. If you could develop some kind of shake that you drink that actually tastes good, you would be giving your body energy and controlling seizures and getting all sorts of health benefits.

We know that anti-seizure drugs have a host of side effects including in kids, they cause developmental days. It can ultimately decrease the IQ of the kids that are following it and have all sorts of developmental delays. If we could mimic the ketogenic diet with ketone esters, I think that’s what I’m most excited about is changing the world of epilepsy with this. A lot of epileptologists will argue well, the ketogenic diet works because it’s restricting glucose and it’s not just the ketones. A lot of the data that’s emerging now is suggesting that the ketones themselves have anti-seizure effects. Ketones have anti-inflammatory effects, tremendous anti-inflammatory effects.

I think a lot of seizures that people are having whether it be caused by febrile seizures or various viruses that cause neuroinflammation, things like the herpes simplex virus, before people get colds or outbreak, they’ll get a headache or shingles. I have people that email me and they say is this the virus that I have in my body affecting my brain because I get these horrible headaches and a few days later, I get shingles. We know that the viruses cause neuroinflammation in the brain and some people who have headaches, they’ll have a seizure. Some people have these various neuroinflammatory disorders.

I guess a good example would be traumatic brain injury. It causes neuroinflammation. If you’ve had a penetrating TBI, a penetrating traumatic brain injury, you’re about 85 to 90% likely to have seizures. There’s seizures because you’re disrupting brain energy metabolism. You are causing neuroinflammation that is undoubtedly contributing to the seizures. [inaudible 00:43:35] is showing you can actually use a PET scan technology and show that just preceding a seizure, people will have higher rates of neuroinflammation. Then when you have a seizure, you have greater levels of neuroinflammations because seizures beget seizures and it could be resulting in part due to this neuroinflammation which the ketones could be targeting.

Orest: There’s a lot of stuff out there in terms of in the supplement world and a lot of it is very poor quality. What exogenous ketones that are out there right now do you find are good quality and produce the effect that they say they’re going to produce? I’ve been taking Kegenix. Actually by the way, if you sign up for them, they have a great ketogenic menu that they send you every day.

Dom: Oh, really?

Orest: Yeah. They send you a recipe for 30 days every day and it’s actually, the food is really good.

Dom: I have their product here so I actually keep it by my desk, yeah, yeah. Yeah, I have their product. Pruvit makes a product too that I’ve tested and tried. I think these companies have made big strides because I’ve been following them all along. Some of them use a formula that we developed and the University of South Florida has the license for it but they have different licensees for the patent. Some of them incorporate a ketogenic formula that has been shown to be superior. It’s a combination of ketone salts and medium chain triglycerides which was incorporated into the Kegenix formula.

I think the ones that stand out, the 3 that stand out would be Kegenix. Pruvit has really done a great job with their product, too. ForeverGreen, they have a product Ketopia. I’ve tested that. All of them tend to raise my ketone levels between 0.5 to 1, depending on the state. If I’m fasted, I feel like my body is using ketones at an accelerated rate. Sometimes they won’t elevate as fast. It depends. They’re now at the point where all of them tastes good actually.

Orest: [crosstalk 00:46:13]

Dom: Yeah, they’re pretty good. This is ketone salt products so a lot of our research, probably about 80 to 90% of it has been the ketone ester. It’s extremely difficult to mask the flavor of a ketone ester. Gram for gram, it’s on average about 2 to maybe 3 or 4 times more potent depending on what ketone ester you’re talking about. The properties can make it difficult to administer because of tolerability, of palatability. We’re working with different types of ketone esters for the special operations community, also for medical purposes. When it comes to commercially available products, I would say Kegenix way top of the list. Pruvit, up there with them, too. ForeverGreen makes the Ketopia product, I think which is … I’ve tested them all and they all give me about the same level of ketones.

Then the other companies like Quest Nutrition that make a Medium Chain Triglyceride oil powder. I keep it also by my desk here. I think it’s also on Amazon, you can get it. I add a scoop to that to my coffee. You can drink a cup of coffee and show a pretty significant elevation in ketones with 1 or 2 scoops in there. That’s a product that I like, a ketogenic product. When it comes to exogenous ketones, yeah, I think the 3 companies, the Kenegix especially is the one that I’m using right now and it’s a fantastic product. I think these companies, I’m pushing them. I’m always pushing them. I was like yeah, we should reformulate it in a way to get this amount of ketones in it so you can reliably get levels to 1 to 2 millimolar

They are always in the process of reformulating and evolving. I think they’re probably going to have to evolve to deal with the competition out there because I think there’s going to be a lot of competition with people trying to get the best product. I’m in the business of actually doing the blood work to show what actually works and what doesn’t work. The 3 product that I mentioned are confirmed by us as ones that actually truly elevate ketones and they happen to taste good too so that’s a benefit.

Orest: Is the amount of exogenous ketones you take dependent on your body mass?

Dom: Yeah. It’s a good question. It definitely is. A hundred and twenty pound female is going to not take the same as a 250 pound male. Interestingly, there are some people that … I’ve seen people that were over 200 pounds get a 1 millimolar boost in taking 1 packet of exogenous ketones. I’ve seen my wife, for example, took the same packet and her levels were 0.5, 0.4 to 0.6, around there. It really depends. Not that the blood levels of ketones is the end all be all because it could be that my wife just uses ketones more efficiently so the tissues are sucking them up and using them for energy or transporting them to the brain.

I think it’s, we call this the pharmacokinetic studies which is you consume the ketones and then you measure the blood at 15 minutes, 30 minutes, 1 hour, 2 hours, 3. It’s a tedious thing to do and you do it multiple times over multiple days but it gives you … That pharmacokinetic profile will tell you how potent that product is. We do a lot of pharmacokinetic studies in mice, in rats, and now we’re doing it in humans. I’ve seen that it varies but on average, yeah. The packets that are out there now are now about 40 grams per packet, 30 to 40 grams per packet, and 1 packet is good for anyone weighing between 150 to 200 pounds, I would say.

I was on a daily routine of taking 1 and a half packets per day for a long time. I was doing an intermittent fasting where I wouldn’t eat all day but in the middle of the day, I would mix 1 and a half packets together and I would drink that over a period about 1 and a half to 2 hours. That would be my window of getting stuff done in time. I would get all my emails and teaching all the way. Then from 2 to 6, I would just be writing or working on grants or just working on high-intensity, mental intensity things. I would get the most work done during that time.

I would sip on it gradually over an hour. If I downed it all in one shot, some of the issues … The mineral load that you get from some of these ketone products, they could have sodium, potassium, magnesium in there. As you know milk of magnesia is a laxative, and too much minerals. I drink a little bit, let it sit on my desk, and then maybe half hour later take another sip and then the mineral load isn’t as much. I find that the buzz that I get is pretty good. These products have a little bit of caffeine. I know the Kegenix has green tea extract which may give you 50, 60 milligrams of caffeine but it’s a nice little buzz.

Orest: You’re talking about the blood levels of ketones. From a practical standpoint, an individual like me or our listeners, how do they know they’re in ketosis? How do they measure it and what level do they want to be at to basically get the optimal effect of exogenous ketones?

Dom: It may vary. If we go to the extreme, to the epilepsy patient or the person who has a metabolic disorder, it could be as high as 3 to 4 millimolar. For the normal person that’s just using it to enhance their energy levels or cognitive state, their physical well-being, I would say anywhere between 0.5 to 2 millimolar would be the ideal level to be at, blood levels. Not everybody has the means or the interest to measure their blood level so you could also use a urine ketone strip. I don’t know if I have some around here. Yeah, I think I do. These are the Multistix here that measure 10 different things. On one of these things is ketone levels. It actually measuring acetoacetate and you have conversion of beta-hydroxybutyrate to acetoacetate.

You can go to a CVS or Walgreens, any pharmacy and buy what’s called Ketostix. Usually CVS has their own brand and it only comes out to, I don’t know, 25 cents a strip. Measuring that if you’re out of trace into the moderate levels, let’s say from the Ketostix anywhere between 15 to 40 milligrams per deciliter, that if your ketones are elevated to that extent or even a little bit higher if you’re exercising, you’re getting the benefits of ketones which essentially means that your blood levels are high enough, that the metabolites are high enough that it’s having a physiological effect. It’s giving your brain more energy, it’s having anti-inflammatory effects that I talked about. Perhaps even effects on gene expression which have been studied in various labs. You’re getting the benefits of ketones if you’re registering on what’s called the P-Strips, the Ketone strip.

The blood is the gold standard that we have now and if you’re measuring 0.5 to 1, you’re getting benefits. For athletes, the optimal level may be as high as 3 millimolar, so 1 to 3 millimolar. The athletes that I talk to do a combination of a modified ketogenic diet or modified Atkin’s and then they’ll supplement prior to or intra workout. They’re doing a hybrid approach to their own endogenous ketone production and in further augmenting their performance with endogenous ketones.

Orest: There’s a few ketone meters out there that measure blood levels. What do you find is the best for everyday use for someone like myself?

Dom: I would recommend the Abbott Labs Precision Xtra. It’s pretty good. Then they have the Abbott Labs makes a … It’s called Precision Neo device. It’s a little bit smaller profile device. Nova Max, we used to have a couple in my lab. Nova Max makes a ketone meter that 5 years ago didn’t work very well but I think they have improved the technology over time. I guess Precision Xtra would be the one that’s most widely available, and Neo is pretty good. That’s the one that I use. Right now, I’ve been using it. It’s slightly more accurate, might be a little bit more expensive but it’s slightly more accurate when it’s measuring, especially when it’s measuring glucose.

Keep in mind that most of these meters, when we tested them against laboratory equipment that measures ketones and measures glucose, the meters actually measure with exogenous are underrepresenting the ketone number. If you’re measuring 0.5, it’s actually a little bit higher. If your glucose is 100, it’s actually a little bit lower than what it’s really recording. I don’t know why the glucose would be low but the ketones may be reflecting on a lower concentration because you have what’s called a racemic mixture in the ketone products on the market now.

It’s not measuring, it’s not fully measuring all the ketones that are actually in the product, the meter isn’t. Some of it gets interconverted over to the other forms. There’s a mirror image of the 2 ketone molecules. You have the D and the L and some of the L gets converted over to the D and the D is measured on the meter. I don’t want to confuse too many people but the important thing is is that if you are measuring 0.5, you’re actually doing pretty good. That means your ketones are actually higher than that, than they reflect.

I know there’s companies like Pruvit an Kegenix are probably going to formulate their products that have just completely the D form of the ketone body. It may be more accurate in reading on the meter. Keep in mind, you got about 25% underrepresentation of the true ketone value with the current exogenous ketones in the market. If you also measure blood glucose which is an important biomarker to keep track of, these meters consistently measure about 10 to 15% higher than they actually are according to measurement with laboratory equipment. A lot of people freak out if their blood glucose is running 90 or 110. That’s actually okay on the meter. That’s pretty good. A fasting blood glucose of a hundred or higher, you’d probably want to bring that down if you could but it’s not an alarming high in any way.

I’ve done health screenings in different states and I remember I consistently … We’ve had type 2 diabetics and sometimes they’d be 300 or 400 milligrams per deciliter, their blood level. That’s high. When you’re talking the average person does not need to get upset if their blood glucose is a hundred because the meter is likely overrepresenting it for reasons I don’t completely understand. I should use a variety of different meters but the Precision Xtra seems to run a little bit high. Then the Nova Max is also another meter that has improved over the years. I think it’s a little bit cheaper, too. I think the strips are a little bit cheaper. That’s another meter. That’s pretty good.

Orest: There’s little difference in terms of men using exogenous ketones and women. Could you go into that a little bit, the difference?

Dom: Well, I guess it still remains to be studied with exogenous ketones especially. Besides our lab, I don’t think anyone else has looked at the effect of exogenous ketones on females. Those studies still need to be done. If we talk about state of nutritional ketosis in males versus females, I have found anecdotally through feedback that I get from males and females and also from our experimental animals that females are more variable in many different ways.

Orest: That’s true.

Dom: It’s true because you do have the extra cycle and that could impact your physiology, your psychology sometimes if your hormones are fluctuating. I think this needs to be appreciated and that females are more or less unique and special metabolic entities that need to be considered because the effect of hormones can have different effects on metabolism. I’ve gotten quite a few emails from people. When you get into the menstrual cycle, some of them actually produce more ketones but more often than not is that it tends to kick your body out of ketosis which would make me think that higher levels of insulin maybe being produced. Maybe they become a little bit insulin resistant, maybe their liver is making more glucose. We call that gluconeogenesis. They’re converting more food to glucose which appears to be happening in most of the women.

Now, how would that influence exogenous ketone supplementation? I would argue or I would suggest that exogenous ketones may actually have a more of a positive effect during the menstrual cycle because if you are a little bit insulin-resistant that we know that ketones can enhance insulin sensitivity. Ketones have a mood-stabilizing effect. Recently, we ran some experiments to show that it reduces anxiety, it helps to stabilize the mood, it helps dampen, significantly attenuate the fear response or stress response. These are all things that can play into, you know, we know premenstrual syndrome or rather psychological effects that could be associated with hormone fluctuations. Maybe ketones could stabilize that.

That’s really how it’s working on the brain in regards to controlling epilepsy is that the leaders in the field feel that the ketogenic diet is preserving brain homeostasis. They use the word homeostasis a lot. It helps bring a dysregulated brain back into normal homeostasis. I think maybe ketones for females could be used for that purpose and I think also females tend to have a lot of raging appetite sometimes during their menstrual cycle. I think the dose that females are using may need to be adjusted depending upon their cycle, and that would really be the only variable. Other than that, I did find a few emails of women that took the product and just blew up and they felt like they’re holding water.

Normally, we’re excreting lots of sodium and for reasons maybe I don’t fully understand, the high sodium content in some of the products, I think the Pruvit product is pretty high in sodium relatively. I’m a big fan of sodium because I think it helps my workout. It helps temporarily increase your blood volume so you get a better pump and more fluid reserves. In females especially if maybe they’re menstruating or their insulin’s high, they all tend to retain more sodium in their bodies and they get that puffy effect.

I would argue that this is more or less a transient effect. It’s a very real effect because some of them show me their scale numbers and it could go up 5 to 7 pounds in the first couple days that they start using 2 or 3 packets of the product per day. Typically after a week or 2, they start shedding the water and it’s like their body is readjusting to excreting more sodium and then they balance out and then it’s like wow, their bodies tighten up again.

I’ve gotten a number of emails, enough feedback to make me realize it’s a real phenomenon that about 20 or 30% of them tend to get a little bit puffy when they start the product because maybe they’re retaining some of the sodium that’s in the product. The sodium is bound to beta-hydroxybutyrate and that’s one of the salts. The Kegenix products, I think, has sodium, potassium, magnesium, and calcium together whereas the Pruvit product is mostly the sodium beta-hydroxybutyrate. Calcium too, it has some calcium.

Orest: On the exogenous ketones, is there a toxic level and do you recommend cycling on and off them or what’s your perspective on that?

Dom: I get that a lot, like should we be in ketosis all the time? I don’t think so. I think it makes sense that from an evolutionary perspective, if we look at our food availability and if we look at the types of food that we’re eating years ago that it’s a natural state of man to be in ketosis, in and out of ketosis during times. Maintaining it all the time, which is what I do actually, may not be optimal but I know I feel better. If you feel good and my blood work looks really good, I see no reason of getting off of it but I don’t like to tell people what to do.

I also think of what we’re doing is breaking new ground. No one, except for people and I do talk to people managing disorders like metabolic disorders or epilepsy and they’ve been on, they been in a state of ketosis for decades, literally decades and their blood work looks fantastic. I would argue that it’s probably not hurting them in any way. I also tell people to, if you’ve got blood work every year or so, I would say get it 2 or 3 times a year instead of once a year or once every couple years. I talk to people and they’ve never gotten blood work in their life.

I think it’s really good to get a comprehensive metabolic panel at least once a year, ideally 2 to 3 times a year, especially when you’re making such a dramatic shift in your diet because it’s really changing the way your body is working. You want to look at kidney function. You want to look at your liver enzymes. You want to look at your markers for kidney function like your creatinine levels. I like to look at hormones, too. Even things like IGF-1 and what I found insulin like growth factor can contribute to things like cancer or perhaps could stimulate the growth of cancer if you have cancer.

I did find that my insulin levels instead of being 3 or 4 are now down to 1 or 2, and my IGF-1 levels are at the low range of normal which I think is probably pretty good going into … Now that I’m in my 40s. As we get older, I think it’s good to keep insulin low that keeps insulin sensitivity high. As we age, we become more carbohydrate intolerant, meaning our bodies just simply don’t use sugar and carbohydrates like it did when we are 19. I grew up in Italian family eating massive amounts of pasta and bread and everything. If I did that now, I don’t know what would happen.

As we age, it’s ideal to shift our bodies into eating more low carb and even being more ketogenic. For a 17, 18-year-old kid to be taking exogenous ketones or being on a ketogenic diet all the time, I don’t think that’s ideal. I think maybe the spikes in insulin help with the growth in many ways and your body is just so insulin-sensitive when it’s younger. I think more protracted sustainment of nutritional ketosis is better if we’re older. I would say not so much for the younger population but I think continuous use for the older population is okay and may be ideal.

Orest: I like to put it all together here in terms of maybe giving someone a regimen, maybe me. I’d lift 3 times a week, do cardio 3 times a week, want to lose some body fat. I’ve always had a issue with body fat. I was always the fat kid in grade school. I have coffee in the morning, I mix it with MCT, actually a couple of scoops of that plus some creatine and coconut oil, magnesium. When do I take the ketogenic product or any kind of exogenous ketone in relationship to the workout? Then when is the best time to actually measure your ketone levels after you take the exogenous products?

Dom: It sounds like you’re doing everything that I would be doing at your age or should be doing now. I do just eat 2 meals nowadays. Sometimes I fast like today, if I have to wake up early. As far as when to take the ketone supplement, I’ve had quite a few emails from older people. I was actually just talking with Mary Newport. You may know her. She advanced this whole idea of ketones for Alzheimer’s disease and wrote the book What If There Was a Cure and it’s a book about ketone and ketone esters.

What I find is that following a regimen like you’re following with the butter coffee or bulletproof coffee, whatever you want to call it, in the morning. Then drinking that and once you get hungry, then it’s time, then you could take your ketone supplement. You’ll probably experience the benefits of ketones as far as energy, appetite suppression, and ride that for a couple hours which I tend to do and try to condense my work into that time. Then eat late afternoon or in the evening for a couple hours and that would be intermittent fasting. In regard to consuming the ketones during exercise, I would do it before and maybe even intra workout. I think some of the benefits of ketones could be experienced, could enhance recovery.

As far as measuring ketone levels, we find that with the Kegenix products and the other products out there that they peak between depending on what’s in your stomach and whatever you’re taking, whether if it’s fasted or with a meal, anywhere between 30 to 90 minutes, so we’ll call 1 hour. Consumption of it usually peaks within about an hour. I find in me, if I’m fasted at about 45 minutes, I hit that just about 1 millimolar. After 45, it starts to come down a little bit depending on what I eat. I would say about 1 hour, you’re in strong ketosis. The products that incorporate medium chain triglycerides has a salt, medium chain triglycerides. That’s extended out a little bit farther and that would include the products that I mentioned, the companies.

Orest: The Quest MCT.

Dom: Yeah, yeah, in the Quest MCT.

Orest: Any pre or intra workout supplements that you find have been helpful to you?

Dom: Yeah. I think branched-chain amino acids are something that I’ve used in the past. I haven’t been using them now. Scivation is the brand that I use. They make a product called Xtend and I really like that product, and you can get the product as sweetened or unsweetened called the raw form. I buy that product. I think branched-chain amino acids have some merit behind it. We know leucine, there’s a ton of research on leucine as a stimulator of muscle protein synthesis. If you’re in a fasted state or calorie-deprived state, if you’re doing a reduced calorie diet to lose weight, to lose fat, I think the leucine may help you preserve and enhance muscle.

Also, branched-chain amino acids have an effect on your exercise performance, so perceived exertion. What they do is block the nutrients and your serotonin at the level of the blood-brain barrier. Serotonin can make your performance, can make you feel tired, can make your performance sink. It blocks that if you take branched-chain amino acids intra workout or before you workout. Caffeine, I would have to say caffeine is one of the best pre-workouts out there in moderation. You take too much caffeine, it could have a negative effect.

In practice, it usually amounts out from a neurological effect as far as feeling in about a hundred milligrams. If you look at the physiological studies, you put someone on a treadmill and run them to exhaustion, it usually takes about 400 to 600 or 500 milligrams of caffeine to get these measurable effects. I just feel too wired with that. I think being in a state of ketosis makes your body more sensitive to things, more sensitive to caffeine so maybe you could probably take less of it. Other than that, I’m not a real big supplement guy. I take vitamin D3, I take a little bit of melatonin before I sleep. Other than that, B12, I have supplement with B12 that I take. Other than that, I don’t take anything.

Orest: Any protein supplements that you like?

Dom: I’m testing different vegan-based protein supplements. I do have a little bit of a dairy allergy, dairy protein. If I drink a glass of milk or have a big whey protein shake, it just doesn’t sit right. It doesn’t agree with me. The vegan protein isolate supplements, protein powders over the years have evolved. Over the last 5 to 6 years, they were horrible 5 years ago. Now, they actually taste pretty good. The one that I use, I think, is MRM, MRM Dutch chocolate protein powder and it’s a combination of hemp. It has rice and pea protein and it’s a combination of the blend. Then it has stevia and Dutch coco and it’s not prepared or processed with various things like hexane. There’s 2 or 3 products that I bought, that’s one of them.

I’m experimenting with some of these protein isolate, vegan protein isolates because I would like to develop a ketogenic eating strategy for vegetarian which is easy because they could eat eggs and dairy products. I’d like to develop a vegan ketogenic diet regimen because there are some people out there that whether they have cancer or epilepsy or they’re just trying to lose weight or get the benefits of the ketogenic diet, they are vegan. I’m not a vegan but I have friends that are and I’d like to be able to develop a protocol that would allow them to have a food selection and even shake recipes that they could use.

These vegan protein supplements have evolved to the point where they’re such low. They’re very low in carbohydrates and some are the whey protein and will allow them, a vegan, to get their protein needs supplied. Right now, I’m not using. The only supplement that I’m using is just experimenting with these vegan protein powders and they’re pretty good.

Orest: In your interviews, you talked about some ketogenic desserts that are out there. Tell us a little bit about that.

Dom: Well, the one that I make actually would be the … Yeah.

Orest: I thought there are some commercially available out there.

Dom: Oh, yeah, yeah. Quest, if you go to, they have a variety of … Let me see. I had a whole bunch in my office right here. I could show you. Actually, I gave a lecture to the medical students, the first and second year medical students, and I brought the box. I was like, “They won’t even eat half of it,” and they quickly consumed all of them. Part of my mission is to connect with the future doctors, the medical students and lecture to them about the benefits of the ketogenic diet. Within that box, there was the ketogenic, more or less the Reese’s peanut butter cup and they have the cups that have mint inside or that have just a chocolate cream inside. There’s Italian crackers. There’s chocolate mousse. I think you’ll find all these on the website.

Over the years, it has been fun working with that company because they send us all the prototype products. It’s literally been years. We’ve been testing these things but it took them … They move very fast on many fronts but they had to do a lot of packaging, studies, and safety studies and shelf life. They have to make sure that they can stick the peanut butter cup at 40 degrees Celsius for a year and make sure the nutritional value is the same after. They had to do all these things before they hit the market. They just hit the market literally this month., if you go there, you could buy a la carte and click on the meals that you want or click on the deserts or the snacks and, it’s just sent to you and you could be on a monthly plan where they send you the same thing every month.

I guess one of the benefits of being into ketogenic diet research is that companies that are trying to get into this space would be like. “Well, I’m developing these foods. Can I send it to you to try?” I’m like, “Sure.” What I do is I do the blood work that goes along with it to make sure. I would say, most of the companies that send me things, about 80% of them, I was like, “No, this is not ketogenic. It might be low-carb but it’s not really sustaining ketogenic.” I deal with a lot of different companies and I like to highlight or talk about the ones that have really evolved to the point where they’re truly ketogenic like Quest Nutrition.

Orest: What’s on the horizon? What do you see coming up here in the next few years or over time here?

Dom: Well, next week, as early as next week, I’m heading off to Banff . There’s the Ketogenic Diet Symposium which is about 600 plus medical doctors, scientists, the Charlie Foundation. Meryl Streep has been to these events and talks. It’s doctors that study cancer, Alzheimer’s disease, ALS, autism, epilepsy, of course, all presenting their data. My lab is going there and they have poster presentations and platform presentations. That happens once every 2 years. We’re very excited about that and we’re presenting there the next week in beautiful [Bath 01:21:37].

Over the next 2 or 3 years, what I hope will happen is that the development and testing of ketone esters will be such that they’re in a palatable form that we can get them to the mass market. As I mentioned, they don’t taste very good right now. That’s one of the major hurdles. Also the safety studies. We’re doing a lot of safety studies now to get them FDA approved. The FDA has a branch to become a safe food product that needs to be generally recognized as safe or [inaudible 01:22:19] and you have to do lots of safety studies before that happens if it’s a new entity, a new molecule to hit the market.

The salts are in a grey area where you have beta-hydroxybutyrate in food. Basically, if you’re eating meat from an animal that’s ketogenic, there’s beta-hydroxybutyrate in it. The salts are found naturally anyway but ketone esters are a little different because they’re not technically found in nature. Over the next year or so, we’re doing a lot the safety studies so we meet that FDA regulation hurdle and also exploring the different applications of ketones which would be the anti-anxiety effects, maybe the effects on anaerobic performance like sprinting is something that we’re interested in studying.

Studying a variety up to a dozen different types of ketogenic formulas, so various types of ketone salts and various types of ketone esters and finding the ones that actually are most potent and the ones that may work better for this disorder or that disorder. That’s a pretty tedious task because first, you develop and formulate the agent and then you do the pharmacokinetics to say yeah, it elevates ketones. Then you take that particular formula and apply it to an animal performance study or disease model and then you take it to humans and do the same thing for performance and whatever. That encompasses a lot of what we’ll be doing in the next couple years.

Orest: Okay, okay. Great, great. Well Dom, we are coming to the end of … A little partially to the end of my agenda here. I want to thank you. Lots of actionable items for our listeners here, lots of things that are very practical that people can put to use immediately as soon as they get that order from Amazon the next day with their prime account. A couple things, the Old Guy does things a little differently. Tim Ferriss has his rapid fire questions that he ask again. The Old Guy, if you’ve been through our website, we’re about virtues and vices. Sometimes I like to find out a little bit about my guest’s vices. What kind of music do you like to listen to?

Dom: Music, wow yeah. I talk about this with my wife a lot. Music can completely change your state so it depends on what state I want to be in. Yesterday, I jumped … One thing that’s therapeutic for me is to jump on my motorcycle, listen to music, and go to the gym. It’s a combination of weights, motorcycles which I’m really into, and heavy metal music whether it be old school AC/DC or Metallica or Guns N’ Roses or Disturbed.

Orest: That’s great workout music.

Dom: Yeah. I get fired up, I get on my bike. I just have a short ride to the gym and it’s just music and the things that I like to do. That’s for when I want to be amped up and want to get a high. If I’m just relaxing with my wife, she’s like Latin music, like salsa. If we’re just chilling out, I listen to even some Christian rock and I’d listen to classical music when I’m driving sometimes. I keep it in the background if I’m working on a grant. I like listening to classical music. It depends on what kind of state I’m in.

Orest: Okay, all right. When you are cheating and eating something unhealthy, what is it?

Dom: Over the last couple years, when I go to the movies, I like popcorn. I get occasionally, maybe a couple times a year will get a big popcorn and I’ll have that. If I’m traveling abroad and if I’m in Naples, I’m going to get pizza. If I’m in Switzerland, I’m going to try some chocolates. It depends but probably dark chocolate, sushi, if you call that a cheat food, I’ll eat the rice sometimes and popcorn. Occasionally, things like pizza. It depends.

We traveled all through Southeast Asia and I ate some food. I don’t even know what I ate, some of it. It was some strange stuff but I know it wasn’t ketogenic and of course, I feel fine actually. Sometimes I’ll get a little buzz and a high if I eat some sugar. Some of the consequences of eating sugar or high carbohydrate foods especially if I eat at night, I wake up a few hour early because I’m so hungry. It spikes my insulin and I wake up out of ketosis and I wake up hungry. A long answer to your question but [crosstalk 01:27:33].

Orest: That’s good. Now, do you have a trash TV show that you watch?

Dom: You know, we don’t even have cable in my house, yeah. For a while, we didn’t even have a TV. Trash TV show, oh you know what I have been watching actually is the A-Team.

Orest: Oh, my God. [inaudible 01:27:57] old school.

Dom: Yeah, the A-Team and Miami Vice and I think Knight Rider. These shows that I grew up watching. I’m a little bit nostalgic about them especially the A-Team. It just happens to come on this obscure channel that I have on a non-cable network. I have the little antenna. I’m picking up some signal from somewhere. I like to watch something that is completely stupid and it just gets my mind off of work and I relax with my wife and we just watch it. Oh, also I guess that would be the trashy channel. Yeah, but sometimes we’ll watch a little bit of travel channel. That’s really the only, and that’s not trashy but yeah. I’ve been watching the A-Team the last couple of weeks.

Orest: All right. Do you drink alcohol?

Dom: Yeah, I do. I brought the last bottle home. Actually, there’s a company called Dry Farm wines. It makes, I would call it ketogenic wine and it’s …

Orest: Oh, my gosh.

Dom: Yeah. Look them up. Look them up. They’re called Dry Farms Wine and I saw it at a recent convention or workshop and I was like, “What is this?” I was like, “You know what, if it really is ketogenic, send me some and I’ll do the blood work.” I drank, they probably have about 20 different wines out. I think what they did is basically pick wines that were very high quality but had very little sugar, like 1 or 2 grams per large glass. When you consume them, my blood glucose is completely stable or goes down a little bit and my ketones don’t budge at all. Maybe they might shoot up a tiny bit just because of the mild hypoglycemic effect.

Essentially, you can drink these wines and stay in nutritional ketosis and it has no effect. Whereas if I have a rosé or some kind of sugary wine or beer, it does kick me out of ketosis. Even like, what do you call it, a Michelob ULTRA will … If I have 2 of them and that’s really my limit, it can kick me out of ketosis. Dry Farm wines are fantastic. I get this question a lot, can I drink wine? People get stressed out. Can I drink wine on a ketogenic diet? I was like yeah, but you really got to do your research and find out which ones have low sugar and test them out.

Now, all the testing’s been done for you because you could just go to Dry Farm Wines. I think they’re reasonably priced. They’ve been sending me wines and I’ve been [inaudible 01:30:47] it but I think they’re good wines, high quality wines at a really good price and they taste great and you can maintain ketosis while you’re drinking them. I don’t drink more. Actually yesterday, I had 2 glasses and that’s a lot for me. I typically drink 1 small glass about 4 ounces, 3 to 4 ounces per day and last night, I had a little more nap but yeah, that’s my typical.

Orest: That does happen. That does happen.

Dom: Yeah, yeah.

Orest: Being in South Florida, do you smoke cigars?

Dom: No, I don’t. I know Ybor City is the cigar capital of the world. I’m not a big smoker at all but when I do walk down Ybor City and get a whiff of it, I was like wow, that actually smells pretty good. Being in the medical field and teaching medical students, I have to advice against any kind of smoking culture, but I will say that the smell of the cigars down in Ybor City if I’m walking by it, it does smell good. It’s something I could get into if I wanted. I’m studying the thing that I’m doing but I have several friends that are good athletes and they go down there and have a cigar every once in a while and I’m sure it doesn’t hurt them.

Orest: It’s a great way to have a great conversation with someone. It takes about an hour to smoke a cigar, and I find it very therapeutic in terms of relaxing and having a nice visit with a friend. All right. Dom, thank you. I’m very grateful for you taking the time. We went well over what I thought we would in terms of the time, but so much actionable information and so much great stuff. It’s just great and I think everyone could get a lot of value by listening to this and probably listening to it a second time. This is Orest the Old Guy from www.oldguytalks signing off. Until later.

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Orest is a 63 year old blogger, internet marketer, standup comedian and health care professional that lives in Phoenix, Arizona with his wife and two kids. When you meet Orest you will be surprised (the cover does not match the man) to find him funny, edgy and very casual, most of the time his filter is often off. His wife and kids often have to tell him to “grow up”. If you piss him off you will find that he can turn into a DICK real fast. Orest REALLY enjoys spending time with his wife and kids!!!!! Drinkin fine liquor and smoking cigars while watching UFC, football and basketball are favorite pastimes. He falls asleep during baseball and soccer. Occasionally he will read a book if there are a lot of pictures in it. For keeping fit Orest likes to lift heavy weights and hike Squaw Peak. If forced too he will do Yoga, actually he got plantar fasciitis in Yoga. Orest is looking to live the next stages of his life full of kick ass shit. He wants to share those experiences with you and wants to hear about yours. Join Orest by signing up to get his 5 Rules Of Life and get regular notifications about Weekday Political Cartoons and other KOOL shit.

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