[Transcript] – A Deep Dive Into Ketosis: How Navy Seals, Extreme Athletes & Busy Executives Can Enhance Physical and Mental Performance With The Secret Weapon of Ketone Fuel

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Podcast from:  https://bengreenfieldfitness.com/podcast/low-carb-ketogenic-diet-podcasts/deep-dive-ketosis-navy-seals-extreme-athletes-busy-executives-can-enhance-physical-mental-performance-secret-weapon-ketone-fuel/

[00:00] About Dr. Dominic D’Agostino

[02:34] Dr. D’Agostino’s Ancestral Health Symposium Research

[10:32] Significance of Using Ketones

[14:13] Can you Get into Ketosis by eating Ketones?

[19:50] Utilizing Ketones in Sports

[24:13] Effects of Using Ketones

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[35:31] Maximizing A State of Ketosis

[44:28] End of Podcast

Ben:  Hey folks, it’s Ben Greenfield here, and if the concept of low-carbohydrate, high-fat eating or ketosis are anything that is of any interest of you, then you are going to absolutely love today’s interview.  A few weeks ago, I was at an event called the Ancestral Health Symposium, and there was a guy there presenting some really fascinating research that he’s been doing on ketones and ketone intake and fat intake and performance, and his name is Dr. Dominic D’Agostino, and he’s a professor at the University of South Florida and he’s doing some really remarkable research.  For example, he’s done experiments on mice where he’s found that a ketogenic diet combined with something called oxygen therapy can literally starve tumor cells, starve cancer cells, since cancer cells feed on glucose, but he’s taking a lot of his research and not just looking at things like cancer but also performance and exercise efficiency and how that’s related to ketosis as well.  And Dominic is actually on the call with us today, we’re going to delve into some of the research that he’s been doing.  We’re going to talk about some of the practical aspects of how you can use some of the findings that he’s come across as far as the use of ketones, the use of a high-fat diet.  We’ll talk a little bit about supplementation, about safety, about carbohydrates, everything.  So Dominic, thanks for coming on the call today, man.

Dr. D’Agostino:  Thanks for having me, Ben.  I appreciate it.

Ben:  So let’s jump into this poster presentation that you did at the Ancestral Health Symposium.  Can you kind of explain the research that you were presenting there so that we bring folks up to speed?

Dr. D’Agostino:  Yeah, sure.  Well the title of the poster, you know what it initially was, prior to the abstract submission, was a project that stemmed from the research that I do funded by the office of Navy research, specifically to kind of enhance the Navy SEAL, war fighter, physical performance, but most importantly, their resilience to the undersea environment.  Navy SEALs use what’s called a closed circuit oxygen re-breather, and if you’re familiar with scuba diving, you’re probably familiar with re-breathers.  Their closed circuit re-breather allows him to breathe oxygen.  There’s no bubbles coming out, there’s a stealth component to it.  An advantage is that it’s very quiet, the disadvantage is that it give you seizures.  So the research that I’ve done is to figure out why the SEALs get seizures using this oxygen re-breather and to develop a mitigation strategy against it.  In the process of doing that, in the process of developing neuroprotective strategies to extend their time underwater, you look at drugs, anti-seizure drugs, and a number of other things that just flat out didn’t work, and the I saw that the ketogenic diet was used for drug resistant epilepsy.  You know oxygen seizures are actually drug-resistant, so I looked into this.  I had a personal interest in the ketogenic diet years ago, and we were able to develop a ketogenic diet in a pill, I guess you could say, and the advantage is that you can circumvent the dietary restriction that was needed to produce elevated levels of ketosis, of ketone bodies.

In our rodent model, we found it to be incredibly neuroprotective, and it prevented seizures from oxygen toxicity above and beyond any drug therapy that we tested, and we come to find out that these ketone bodies are a very efficient source of energy, so ketones in old literature were thought of metabolic poison, but we know that they’re a form of energy that can be used by almost all cells in the body.  Actually cancer cells can’t use it, but that’s another story.  So recognizing this, we expanded our applications beyond the Navy SEAL stuff, and we looked at things like Alzheimer’s disease.  We had a paper come out last week on that.  Cancer, ALS, and this was all rodent model stuff.  After the abstract submission to ancestral health, I did some just very preliminary work in humans, and I was taking it myself and a couple of friends were.  On the poster actually, Peter Attia did some research.

Ben:  And by the way, when you say you were taking it yourself, you were saying that you weren’t just say like eating a high-fat, low-carb diet to induce ketosis.  You were actually consuming ketones?

Dr. D’Agostino:  Yeah, well I practice low-carb diet, and so I’m always in some state of mild ketosis, and if I measure my ketones, I’m almost always above 0.5.  You know, it’s kind of an arbitrary definition, but it’s kind of thought that if you’re above half a millimolar of ketones, you’re kind of in nutritional ketosis.  So I always have some level of ketones unless I intentionally eat carbohydrates to get out of ketosis.  When I take oral forms of ketones, depending if it’s a ketone ester or a recently developed ketone salts or even MCT oil, probably the most potent would be caprylic acid and a carbon medium chain.  So either one of those or a combination of those things can artificially elevate blood ketone levels, and in essence, you’re elevating a blood level of a very efficient metabolic substrate that can improve and augment performance, and it crosses the blood brain barrier.

When you’re on a ketogenic diet or you fast, you break down fats, but they can’t readily cross the blood brain barrier, ketones do.  So you’re giving your brain an alternative form of energy that can potentially enhance cognition.  When it comes from an oxygen toxicity thing, we know that high oxygen actually impairs brain energy metabolism, so the ketones can preserve brain energy metabolism in the face of an oxidative challenge, which would be hyperbaric oxygen, breathing oxygen in a hyperbaric environment.  Basically it hits your brain with a big load of oxidative stress, free radicals are produced, and you have impaired brain metabolism, and the ketones prevent that in ways that we don’t fully understand but one way I think is that it’s just really giving your brain, it’s juice in your brain up and protecting it and preserving the brain metabolism.  But it’s also directly inhibiting some of the reactive oxygen species that we see.  There seems to be a direct antioxidant effect, the ketones, and also if you’re enhancing mitochondrial efficiency and mitochondrial function, you get less of the reactive oxygen species being produced.

Ben:  So in the state of low oxygen availability, such as you might see in like these Navy SEAL divers.  You know obviously, the use of ketones or being in a state of ketosis sounds like you can help tremendously in that situation, but what about in a state of low-oxygen availability such as during exercise?  You know, say for somebody riding a bicycle or running or something like that, do you see similar effects?

Dr. D’Agostino:  Or even altitude, yeah.  That’s a good question, and what we’ve shown, preliminary data shown, that there’s an improvement in work output per oxygen molecule consumed.  So one could hypothesize, based on our preliminary data that you have improved oxygen efficiency, so you would be able to essentially derive more energy from the food that you’re oxidizing, the calories that you’re oxidizing.  This is of interest to the Air Force, aviation medicine.  I’m kind of working with working with some folks to develop and experimental model where we create hypoxia, and then we look at motor performance and we look at cognitive performance, with and without ketones, and it will answer the question if ketosis can confer hypoxic resilience, you know?  And just producing hypoxia, low levels of oxygen, and that would have implications, too, for exercise.  If you’re improving oxygen efficiency by enhancing mitochondrial efficiency and delivering an energy substrate where you can just generate more energy from the given amount of oxygen.  Also ketones have a property that we’re now, one of the projects we’re doing is a wound healing project, and we use a Dopler blood flow measurement.  It dilates the vessels to where we get blood flow to where it’s most needed, and there’s a vasodilation effect that we’re just starting to understand.  So that’s another, so you could have improved oxygen delivery, and that’s another thing.

Ben:  Interesting, so can you explain why it is that ketones could cause this kind of effect, why is it that using something like ketones as a fuel versus using something like glucose, say on a brain level or on a cellular level, why is it that it would actually cause something like that to occur?

Dr. D’Agostino:  Okay, we’re following a standard diet, right?  Going back to the brain, it uses glucose as its primary fuel, and in the absence of glucose or reduced glucose availability, the brain has the metabolic flexibility to adapt to using ketones.  If you go to a ketogenic diet, your brain kind of has no choice, right?  You kind of deplete your carbohydrate stores, your liver glycogen gets low, and you start pumping out ketones to kind of reverse this decrements of brain energy.  That’s probably the main function.  Answering that question, I think what it comes down to is that you’re just supplying an alternative form of energy to the brain and your tissues, and your body and your brain is pretty set up to adapt to use glucose well, and it probably maximizes the transport, the utilization and the metabolism of glucose.

Those mechanisms are kind of maxed out, so with ketosis, you’re delivering kind of like a new metabolic fuel at pretty high concentrations, and we’re talking millimolar concentrations, so that’s like a significant source of energy that the tissues are now seeing.  And from an evolutionary perspective, if you could probably argue that we have these mechanisms built in, the monocarboxylic acid transporter, to be specific in our tissues.  So we can readily take up these ketone molecules and oxidize them in the mitochondria for energy.  So from my perspective, it’s more energy, so you have an energetic or metabolic substrate.  You have early experiments done in the heart that how you have enhanced mitochondrial efficiency, so the Delta G of ATP hydrolysis is higher for a ketone per carbon molecule than glucose.  So it’s kind of like a super fuel, you could say.  It’s been coined.  And then you have things like if you look at nutritional physiology, is it enhancing blood flow?

So we get more blood flow to the muscles to the brain, we have physiological parameters that could be altered in a way that can enhance cognitive function and motor performance, so I kind of see more energy, mitochondrial efficiency and physiological parameters that we fully don’t understand yet like brain blood flow or perhaps it’s upregulating a buffering mechanism.  Jeff Volek did some work showing that branched chain amino acids are elevated which would have implications if you’re training hard, having an anti-catabolic effect.  You know the ketones do to, so I think the ketones definitely, even from an illusionary perspective, we stop eating.  Our catabolic pathways are activated.  Gluconeogenesis were breaking down a lot of muscle for energy until the ketones are sufficiently elevated, and the ketones have an anti-catabolic effect and they help you preserve your lean body mass in the face of starvation or in the face of low glucose.  So there’s many different things to talk about, but I think it’s not one or the other but a combination of things, kind of working together.

Ben:  So let’s say that somebody was perhaps wanting to actually do something similar to what you had done in some of these studies and ingest ketones.  So rather than simply go on a high-fat, low-carb diet and generate ketones via the use of fatty acids, you know?  If you’re burning fatty acids and generating ketones as a byproduct of that, what if someone actually wanted to ingest ketones.  Are those available as supplements right now on the market?  Are they FDA regulated?  I mean how would somebody actually go about doing something like that?

Dr. D’Agostino:  Yeah, that’s a good question.  Well a couple of questions kind for come out of that question as does exogenous ketones have benefits above and beyond nutritional ketosis which is achieved with carbohydrate restriction?  That’s a big question that I get a lot actually.  In our experimental models, absolutely.  You know, we’ve definitively shown that you give a high-carb diet to an animal and you give them a ketone supplement, and you get some really fascinating neuroprotective properties.  So my answer is yes, it definitely confers a benefit above the ketogenic diet, but I think that the benefits that you get from giving exogenous ketones will be enhanced if your body is already keto adapted.  If you’re already following a low-carbohydrate diet, you have transporter mechanisms already upregulated.  The help exogenous ketones work.

Ben:  So what you’re saying is that somebody who’s eating a standard American diet, or is eating a high-carbohydrate diet, couldn’t just say hack their way into ketosis and find themselves extremely metabolically efficient just by say like drinking ketones?

Dr. D’Agostino:  They can, but I think yes.  This is a question that I want to answer actually.  From my perspective, yes.  That can occur, and we see it in animal models.  I think the message that I want to get across though is that if we’re going to use ketosis as exogenous ketones to hack the system to get more energy, I think that if our bodies are keto-adapted, meaning that if we’re on a carbohydrate-restricted ketogenic diet, our brain and our body are going to be used to seeing these ketones.  Also elevated ketones produce a mild metabolic acidosis that has to be dealt with, and I think if you’re slamming exogenous ketones, your body’s not used to seeing these ketone bodies which have a mild acidic load on the body.  It’s going to be a little bit harder to buffer, and there’s probably a sweet spot, right?  And I think it’s going to vary between each person.  I think their tolerance and the benefits that they derive from exogenous ketones will vary between each person, and depending on exercise, depending if they’re elite athletes.  I think elite athletes will benefit more ’cause they’re just used to going in and out of ketosis which exercise can do that, but I think there’s going to be a sweet spot.  Regardless, I think adding any amount of elevating your blood ketones will definitely increase performance, but it’s going to be up to the end user and do some self-experimentation to figure out what’s optimal and how to do that, and there’s various ways to do it.  So there’s MCT oil and there’s caprylic acid which is a fractionated MCT.  Its most ketogenic, and we have these ketones.

Ben:  And both of those are in liquid form, right?

Dr. D’Agostino:  Liquid form, yeah, and recently, the ketones that I had on the poster there, the study that we did was there on the market now as a product called KetoForce.

Ben:  So that’s an actual supplement that you can buy called KetoForce.

Dr. D’Agostino:  That’s a supplement, yeah.  It’s essentially ketone bodies that are combined with minerals, monovalent, divalent, cations.  So you’re buffering a ketone body with a mineral, and I think there’s some advantages.  Not only is it feeding ketones, you’re kind of giving your body a buffering system, and sometimes on a ketogenic diet, it just has a natural diuretic effect, so we tend to lose some minerals that are important like sodium, potassium, calcium, magnesium especially.  And the company that has the KetoForce product, prototype nutrition, the chemist there, Patrick Arnold, he’s very innovative and develop some very innovative products.  And working with him on other projects that I had, he’s been able to really come up with some novel compounds that can have a lot of not only therapeutic potential but enhancement of exercise performance potential.

Ben:  Interesting, do you know of athletes and stuff who are using that stuff right now?

Dr. D’Agostino:  Yeah, I know a few.  I’m in contact with them ’cause it’s such a new product then there’s not a whole lot of feedback on it, and the feedback that I’m getting is very positive.  It’s sold under prototype nutrition, and I think there is a good reason for that.  It is a prototype, it’s very new on the market.

Ben:  Is it like for somebody who’s competing in say like a sanctioned event, like if you were doing an event that was sanctioned by the World Anti-doping Association or something like that, is the stuff even legal?  Like can you drink ketones, and I mean is it just as say legal as using MCT oil or coconut oil?

Dr. D’Agostino:  At this time, from what I know and I’ve inquired about this topic because there are ketone esters that were developed and used at Oxford University, and the results show, without a doubt, there was a performance benefit.  I’ve been in contact with some people that I’ve discussed this with, and from my knowledge that it’s not banned at this time, and it would be kind of hard to test, too, ’cause what if you’re doing just a ketogenic diet.

Ben:  Right, I mean that’s the thing.  It’s like you have to just go out and do an Ironman triathlon and eat barely any carbs and be in the state of ketosis, or you could eat a decent amount of carbs, consume a bunch of ketones and also be in a state of ketosis?  So you could almost kind of achieve the best of both worlds if you figured out how to use this stuff properly, right?  And that you could maintain elevated glycogen levels, but then you could also maintain kind of like the focus and the mental advantages of being in the state of ketosis?

Dr. D’Agostino:  With glycogen sparing, definitely, and that’s the advantage of the carbohydrate-restricted ketogenic diet is that it forces your body from a glucose-based metabolism to a fatty acid and ketone metabolism.  And in doing so, it will help your body spare muscle and liver glycogen with prolonged exercise, so it delays the bonking that’s going to happen.  And also one big advantage, it might not be talked about much.  I think you’ve probably already seen it, it’s that emerging interests will be on the brain.  I mean if we can get the brain to perceive that we’re not in trouble during prolonged exercise.  I studied the neural control of autonomic regulation for my PhD, and I’m aware of autonomic mechanisms that if they’re kicked in, our bodies will shut down pretty quick.  And even our bodies have the capacity to keep going, especially skeletal muscle which is extremely plastic and adaptable and resilient.

The skeletal muscle is, and I think there’s autonomic mechanisms in our brain in place to shut us down and to stop, and I think ketones can decrease proceed exertion, and we know that those early studies were done and I’m doing studies right now.  If you can put someone into severe hypoglycemia to the point where it would be put them into a coma and probably be fatal and their blood glucose would be at that level, but if ketones are available, there’s no signs of hypoglycemia and, there’s no decrements in performance.  You know I’ve gotten my glucose down to under 30.  I’ve gotten it down to where the meter doesn’t read it, like it just flashes below, and I felt perfectly fine giving lectures, when I’ve been perfectly intact, and I don’t know if any available substance on the market that would be able to do that.  You know ketones really preserve brain metabolism, and therapeutic implications are tremendous for insulin shock or hypoglycemic shock.

Ben:  So with MCT oil, you could have a diaper day, if you’ve taken too much MCT oil.  Do you get similar, unsafe, kind of territory if you were to say consume ketones as an energy source rather that going after an MCT oil.  Like does it harden your stomach, do you feel strange in your head?  What’s unsafe about this?

Dr. D’Agostino:  Well I’ll tell you my perspective and the feedback that I got.  The ketones that are now available in the market, the ketone body is actually combined with a mineral, and when you ingest it, it puts a mineral load on your stomach and there could be an osmotic shift, if you will of fluid, into or retention of fluid into the gut which could definitely give you diarrhea, it could definitely stimulate peristalsis combining the Keto salts or KetoForce with a fat like, for example, MCT oil or maybe some other kind of fat can delay gastric emptying and I believe it can enhance the uptake and absorption of the ketones.  So I think there’s like a synergism going on there if we combine a KetoForce product with some type of fatty acid or triglyceride like MCT oil.  I think there’s a benefit there.

Everyone will have a tolerance level, they’ll likely be kind of like with drugs, right?  You get this bell-shaped curve, and there’s probably a sweet spot on that curve and that’ll probably depend on your tolerability to it.  After using the product for a while, what I’ve seen is that I can tolerate a lot, so I think our stomachs can upregulate transporter mechanisms that can ultimately prevent a lot of the gastric problems we’re having.  So I’ve probably doubled the amount that I could tolerate when I started a few months ago, so I think we can build tolerance, and I think I found it.

Ben:  How much do you take?  Like if somebody were to get their hands on ketones or KetoSalts rather than MCT oil or whatever.  Is there like a gram or like a number of tablespoons per hour or anything like that?

Dr. D’Agostino:  I think a safe place to start, I find that people have very tolerance to MCT.  Someone can take a teaspoon and be in trouble, or other people can get five teaspoons.  So I think it’s good to start low, and I think it’s going to vary between people.  I think it’s safe for me and like a large male, especially if you’ve had MCT before.  One tablespoon of the KetoForce, what’s that?  Like 15 milliliters, and I usually do things in milli.  So like 20 milliliters of a ketone salt and 20 milliliters of a quality MCT oil.  I use one called Biporilo Nutrition, its pure caprylic acid.  You get the highest ketones, so like a one-to-one ratio of that and with a lot of water.  So the ketone salts will produce a lot of minerals in your gut, so you want to buffer that, so I tend to drink a lot of water before.  I actually take some branch chain amino acids.  Amino acids are kind of good buffers, too.  So I take 20 milliliters of MCT, 20 milliliters of KetoForce with five to ten grams of branched chain amino acids and slam that with lots of water, and then I brew up some coffee with a little bit of butter and maybe a little bit of MCT in it and sip on that over another hour or so, and then shortly after that, I’ll go to the gym.  I’ll go exercise, and I think the ketones are kind of maxing out at about two or three hours.  I think you get the most benefits, and I like to kind of take advantage of the benefits when I’m sitting at my desk and just pounding out a lot of emails or working on a paper.  I seem to have the most mental energy.  Later in the day, when my ketone levels are kind of elevated naturally from a diet but also artificially with a little bit of supplementation.

Ben:  Right, this is something that somebody who wasn’t even exercising could use for mental performance at the office by inducing a state of ketosis just during the day?  Interesting.

Dr. D’Agostino:  Yeah, there’s a lot of talk about coconut oil feeding the brain and delaying Alzheimer’s or for treating Alzheimer’s.  We know that coconut oil is about 60% MCT, and the most ketone production you can probably get from coconut oil is like 0.3 to 0.4 millimolar, maybe 0.3 millimolar actually.  You know, you can get 10 times that amount with a ketone salt and definitely higher even if you combine it with an MCT.  So it’s a pretty potent way to elevate ketones, and there’s been a lot of discussion and even research on ketosis for that disorder, Alzheimer’s and so.  There’s definitely cognitive benefits, actually it’s been shown I think Henderson in 2008 showed a product called AC1202.

The name was kind of technical sounding, but essentially, this AC1202 product was caprylic acid which is MCT.  It caused an increase in cognitive function in people with mild cognitive impairment, so it’s not a drug and it’s now sold as a medical food called Axona.  But the early study that legitimized it in a double blind placebo-controlled study showed that 20 grams of an MCT, which was caprylic acid, enhanced cognitive function, and that was published, and then Mary Newport actually, the woman that I know, she’s a pediatrician and she gave her husband coconut oil, and he had a positive response to it and wrote a book about it.  There’s been a lot of publicity there.

Ben:  What’s the name of that book?

Dr. D’Agostino:  The book is called, I have it on my desk and actually Mary will be a guest speaker in my class.  The book is called “Alzheimer’s Disease: What If There Was A Cure?:The Story of Ketones”, and it’s been a bestseller on Amazon.

Ben:  I’m going to put a link to that in the show notes, I’ll find it.

Dr. D’Agostino:  Great.

Ben:  “Alzheimer’s Disease: What If There Was A Cure?:The Benefits of Ketones”?

Dr. D’Agostino:  “The Story of Ketones”.

Ben:  “The Story of Ketones”, okay.

Dr. D’Agostino:  Dr. Mary Newport, she’s a pediatrician.  Kind of lives in the Tampa area, where I’m at.

Ben:  Okay, cool, and the name of this supplement you were talking about is called KetoForce?

Dr. D’Agostino:  KetoForce, yeah.

Ben:  And that’s just straight-up ketone bodies in the form of keto salts.

Dr. D’Agostino:  That’s the purest form of ketones you can buy on the market.

Ben:  And is that beta hydroxybutyrate? Is that technically the type of ketone that is?

Dr. D’Agostino:  Yeah, that’s beta hydroxybutyrate.  It does convert pretty quickly we find in myself and in other and in our animal studies that it converts to acetoacetate, so beta hydroxybutarate actually need to convert to acetoacetate to be used in the tissues.  So if you measure the urine ketone sticks, it’s important to know that’s acetoacetate measurement, and the blood monitors that people use, that’s beta hydroxybutyrate.  So what’s interesting is that if you get your beta, if you get beta hydroxybutyrate elevated with a carbohydrate-restricted ketogenic diet, sometimes acetoacetate isn’t elevated, but the salts really have elevated my acetoacetate pretty high.  The point I want to get across is that people have a different ratio of beta hydroxybutyrate to acetoacetate, and it varies between two to one to like five to one, beta hydroxybutyrate to acetoacetate, and there’s something going on there.  Actually I’m interested ’cause acetoacetate seems to have the anti-seizure effects, so I’m actually interested in that.  I do work with ketone esters which are even a more potent form of these salts here, and although FDA regulations would be problematic for the ones that we’re working with ’cause they’re pretty potent.  We developed esters of acetoacetate, and they have unique properties over a beta hydroxybutyrate, at least when it comes to brain neuroprotection and seizures.  So we’re working on finding out why that’s the case.

Ben:  And then this other stuff that you mentioned, I just want to make sure I get resources for everybody in the show notes.  The caprylic acid, that MCT oil was a source of caprylic acids, but if someone wanted to get caprylic acid, could they just get caprylic acid or do they need to buy MCT oil or are those terms kind of synonymous?

Dr. D’Agostino:  So caprylic acid is an MCT oil, its 8-Carbon Triglyceride, and if you go to the store right now and buy MCT oil, it’ll probably be about 50 to 60%.  Roughly 50% MCT or caprylic acid, and caprylic acid tends to be the most ketogenic of the MCT oils.  To get the highest boost in your beta hydroxybutyrate levels, pure caprylic acid would be ideal, and that’s sold.  The only place that I know that sells it is Parillo Nutrition.  John Parillo is kind of an old company, and Cat Tree is the product.  And they’re kind of low profile, they don’t advertise much but they supply our caprylic acid for our research.  It’s the one that I use and the one that I favor because I know its pure caprylic acid.  We also do studies with just MCT and that has an 8-Carbon caprylic and also a 10-carbon which is called capric acid, and some studies have shown that there’s a benefits to capric acid for seizures and for other things.  So it’s like you have all these things and you want to test them, and so it’s like okay, I’ll test the MCT, but then I have to taste a fractionated, purified MCT oil.  So we’re running a variety of studies to really tease out and determine what’s optimal, and then you use one dose, right?  And then you’re like okay, well did I use the dose that was optimal?  And then you have to go back and do a bunch of doses to figure out where the sweet spot is.

Ben:  Gotcha, so if somebody wanted to, and I know we’re running up against time, but I want to finish up with one kind of practical overview for people.  Let’s say, I wanted to maximize my state of ketosis.  I’m going to go on like a two to three-hour bike ride.  What you’re saying is you would begin by drinking a decent amount of water, what do you do like 20, 30 ounces of water around there or like a water bottle full of water?

Dr. D’Agostino:  Yeah, I kind of get some water in my stomach prior to ingesting the ketones.

Ben:  And then you would take like one to two tablespoons of ketones?

Dr. D’Agostino:  Yeah, a safe bet for a newbie coming into this is to do 15 to 20 milliliters of an MCT, which would be like a tablespoon and then an equal amount of the keto force product.

Ben:  Okay, so equal amounts of ketones and MCT oil basically.

Dr. D’Agostino:  I, for my experience, yeah.  That’s optimal.

Ben:  Okay, and then would you repeat that, like during an actual exercise?  Could you repeat that on like an hourly basis or would that just be enough to take you through it several hours?

Dr. D’Agostino:  I think about two hours would be optimal, under two hour?  I don’t think every hour is necessary.

Ben:  Redose with that one tablespoon, like one to one ratio of ketones to MCT oil, like every two hours or so like during something like a long bike ride?

Dr. D’Agostino:  Yup.

Ben:  Have you found that there is a limitation in terms of intensity?  Like do you need to keep things aerobic, or if you’re going to go glycolytic, do you need exogenous sources of carbohydrate or anything like that?

Dr. D’Agostino:  For me personally, I’m very sedentary actually.  I get to the gym maybe once or twice a week, and I kind of do some stuff around my house when I don’t go to the gym.  So lately, I haven’t been doing a whole lot of aerobic activity, but anaerobically, I just basically take it on my way to the gym or a couple of hours before if want to kind of take advantage of the cognitive effect and work.  And I find that your ketones are elevated for two to three to four hours at least after, make it five and six sometimes.  The oil, I think the MCT oil can delay the gastric emptying, so you have elevation of ketones a little bit longer.  Branched chain amino acids are another thing that I kind of add into the mix personally.  I think it helps prior to exercise, it can delay exercise fatigue and has some anti-catabolic effects, so that would be the stack that I use.  I don’t use many supplements.

Ben:  It sounds very similar to the stack that Peter Attia and I kind of developed a stack for me for Ironman Hawaii.  It’s what I ended up using kind of like during the first half of the bike ride at Ironman Hawaii.  It was a stack of branched chain amino acids and MCT oil.  He had suggested that I add the ketones into that protocol as well, but my life was so crazy leading to Ironman Hawaii that I didn’t have a chance to test out that component, so I never actually added that in.  I’ve got that on the radar in the future, but it worked out great, and then I got to the special needs turn around where I had a second bottle of MCT oil and branched chain amino acids and everything, and I made a tactical error of allowing that to sit in the heat for about four to five hours while it was waiting for me in my special needs station, and for anybody listening in, MCT oil once it’s heated to about 90 degrees or so, it doesn’t taste so good.  So I ended up switching to on-course nutrition, at that point, but for about the first 60 miles or so of the bike ride, yeah, that stuff was like rocket fuel, the combination of branched chain amino acids, like high-dose branched chain amino acids with the MCT oil, and I can only imagine if I’d have added ketones into that, the added effect.  So this is cool stuff, I really think, let’s just say it goes way above and beyond Gatorade, right?

Dr. D’Agostino:  Yeah, do you take any stimulants by the way, like caffeine or any kind of stimulants?

Ben:  Yeah, so I use one supplement called X-2 Performance, it’s a little bit of caffeine which obviously helps to utilize fatty acids a little bit.  It’s also got some pinitol in there to drive substrate into muscle tissue and disodium ATP to top off ATP stores a little bit more quickly, and then I also use oxaloacetate which helps me to convert lactic acid into glucose more quickly, since I’m not taking in much in terms of like exogenous sources of glucose.

Dr. D’Agostino:  Where do you get that from, Ben?

Ben:  I get that from Dave Asprey, it’s actually something he markets as an anti-aging supplement, but I was speaking with someone at his biohacking conference down in San Francisco who kind of gave me an approximate dosage to use it as like basically to upregulate the cori cycle, and so I take a few of those prior.  As far as other supplements, I mean I use some other stuff that’s not really for ketosis, per say, but just for general heath during the event.  Like I take some adaptogenic herbs and rhodiola cordyceps, stuff like that, but yeah.  Kind of the biggies that I toss in to enhance the ketosis effect is oxaloacetate and the X-2 Performance.

Dr. D’Agostino:  That’s interesting, so that’s a TCA cycle intermediate, and then you could make a salt of that.  So what you’re probably taking is a salt of oxaloacetate maybe.  The Venogen, I know is they have a trademark on that, but there’s other TCA cycle intermediates that you can make a salt or an ester out of, and I think there’s a lot of potential there that I’m working on now, for actually ALS and some other things.  I know the applications are pretty broad.

Ben:  At some point, that’s one thing I do with Pacific Elite Fitness.  It’s not really a supplement company that I run as much as it is a solutions company where I’ll take a bunch of things that are meant to enhance hormones or enhance endurance and kind of just put them all together in a box and ship them to folks.  It’d be interesting to kind of develop just like the ultimate cocktail of all this stuff and just order it to my facility and figure out how to ship it out to people as like a box.  It’d probably be a pretty expensive box, but it’d be cool to figure out rather than people having to go to the four corners of the planet to find all this stuff.

Dr. D’Agostino:  If you train with it, but then you can kind of maybe use it sparingly when you train, and then you just use it for the big event, you know?  Maybe something like that.

Ben:  Yeah, exactly.  No I think its super cool.  Well man, I could talk to you for hours, and I’ve got a ton of notes right now in the show notes.  For people listening in, if you go to bengreenfieldfitness.com in the show notes for this interview, first I’ll put a link to a bunch of the interviews we’ve done with Peter Attia because I know Dominic and I kind of dove right in without really explaining ketosis too in-depth, and so you may want to go back and listen to some of those interviews if you want, more like an introduction to ketosis.  I’ll put a link to the other stuff that we talked about to that book that Dominic mentioned and also to Dominic’s website over at the University of South Florida, so yeah.  We’ll put lots of links in there for you to explore more, and of course if you have questions which I would imagine you do, leave it as a comment in the show notes to this podcast, and I’ll be sure to hop in and answer your questions too.  Dominic, man, thank you.  That was super cool.

Dr. D’Agostino:  Thank you, yeah.  Pleasure being here, you’re definitely an innovative guy out there and really pushing the limits of human performance, and I could see this is like one of the most interesting websites that I came across on human performance.  I recommend it to everyone that I know is interested in this topic.

Ben:  Cool, that’s good to hear man.  Alright folks, that’ll about wrap it up for today, so until next time.  This is Ben Greenfield and Dominic D’Agostino, hopefully I’m pronouncing your name approximately.

Dr. D’Agostino:  Dominic, yeah.

Ben:  Dominic, I like my pronunciation.  It sounds more European.

Dr. D’Agostino:  I get that a lot.

Ben:  Dominic.  Anyways we’re singing out from bengreenfieldfitness.com, have an awesome day.

Prepare to have your mind blown as today’s audio podcast with Dr. Dominic D’ Agostino takes a deep dive into ketosis – showing you how navy seals, extreme athletes and even busy executives can enhance physical and mental performance by using the secret weapon of ketones.

During this interview with Dr. D’ Agostino, you’re going to discover…

-Why extreme Navy Seals are using ketosis…

-Can you get into ketosis by eating ketones (and still consuming high amounts of carbohydrates) instead of eating a high fat, low carb diet?

-How ketosis can be used to control diseases such as cancer, Alzheimers, ALS…

-The mechanism by which ketones can “juice up your brain”…

-How ketosis can enhance blood vessel dilation and wound healing…

-Whether the consumption of ketones is actually safe…

-How to improve your oxygen efficiency with ketone intake…

-Why ketones can be used to enhance mental performance and not just exercise function…

-Practical ways you can use keto salts and ketones to enhance physical performance…

-And much more!

klpDr. Dominic D’Agostino, PhD (pictured right) is an assistant professor at the University of South Florida College of Medicine.

He teaches courses in molecular pharmacology and physiology, and maintains involvement in several studies researching metabolic treatments for neurological disorders such as seizures, Alzheimer’s, ALS, and cancer—all of which are metabolically linked.

His entry in to this field began when, in 2007, the Office of Naval Research funded his study into seizures related to oxygen toxicity experienced by Navy SEAL divers using closed-circuit breathing apparatus. At this juncture, he came across the ketogenic diet, which has already been confirmed as an effective treatment for epilepsy and a variety of seizure disorders.

He is now studying how this same ketogenic diet and the use of ketones can be used to enhance physical and mental performance.

Resources discussed in this episode:

-The book: Alzheimer’s Disease: What If There Was A Cure? The Story of Ketones

-Supplement: Ketoforce

-Supplement: MCT Oil

-Supplement: Caprylic Acid (also available in MCT Oil)

-Supplement: Oxaloacetate

-Supplement: BioSteele Branched Chain Amino Acids

Additional Listening:

If you aren’t too familiar with the concept of ketosis, or want to review other content I’ve produced on this topic, you may also want to review the following:

The Official “Ask Me Anything About Ketosis & Ironman” Premium Podcast with Ben Greenfield.

Combining Low Carb And Extreme Exercise – The Official Results Of The Great Ketogenic Ironman Experiment.

Is It Possible To Be Extremely Active and Eat A Low Carbohydrate Diet?

How To Turn Yourself Into A Fat Burning Machine By Fasting For 24 Hours Then Going Out And Do Monster Workouts Without Bonking.

How To Customize Your Diet.


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