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Dave:             Today’s cool fact of the day is: your brain has a hard time distinguishing between metaphors and reality. That’s why if you do something as simple as clipping your resume to a heavier clipboard, when someone looks at your resume they’ll actually assume that its’ more serious because, subconsciously, we think of serious situations with gravity, or as weighty issues. They’ve actually done studies with identical resumes on different weighted clipboards and found out that it’s a meaningful, impactful variable on how people read the resume itself.

Hey, everyone. Dave Asprey, Bulletproof Executive, here with Bulletproof Radio. Today’s guest is Dominic D’Agostino. He’s an assistant professor of molecular pharmacology and physiology at USF Health Morsani College of Medicine and one of the guys I really look to for knowledge about ketosis: that fat burning stage that we try to be in the Bulletproof Diet most of the time, but not all of the time. We’re going to pick his brain today about how it actually works, the benefits of ketosis, the risks of ketosis, etc.

He’s presented at TEDx and done a ton of different studies looking at metabolic disorders, Alzheimer’s disease, muscle wasting, cancer, oxygen toxicity, all kinds of cool stuff that you might not think applies to you if you just want to feel good all the time, but it turns out the things we’ve learned by looking at the corner cases really help us know more about what’s going on on our end.

It looks like you work out a bit. I’ve seen some pictures of you; I’d say you’re a little more muscular than the average guy. Would you say that’s true?

Dominic:      Maybe, yeah, I guess so. I work out; it’s part of what I do, although I don’t have a whole lot of time nowadays. Powerlifting was a big part of my college days and I do network pretty closely with the natural body building world and have a few close friends that are tied to that community – so definitely an interest there.

Dave:             At the same time, you’re into the keto diet, or different ways of going into ketosis. Are you in ketosis all the time?

Dominic:      I think so. Pretty much, unless I sleep on my diet, unless I eat something out of the ordinary, but generally, yeah. If you measure my blood ketones it would show that I am in ketosis 95% of the time or more. Sometimes I overeat on protein or occasionally I’ll go out to the movies and have popcorn, but that’s pretty rare. Special events.

Dave:             GMO popcorn, nooo! 95% of the time.

Dominic:      Yeah, pretty much. Obviously it’s my research field. I do it for practical reasons too because staying in ketosis keeps me from getting hungry. I eat two meals a day spaced roughly about 12 hours apart. I come from a background of eating like six meals a day and I can’t imagine going back to that pattern of eating or having the time or patience to do all the food preparation and the shopping and everything involved in eating multiple times a day, which a lot of people feel that they need to for performance – but I know that’s not the case.

Dave:             You and me both. The idea of many meals a day is exhausting and just why would you? Can you summarize your research? I did my best; I mentioned some of the fields.

Dominic:      You did good.

Dave:             But for people listening, imagine they’re driving; imagine that half of them have heard of ketosis. The other half may be interested in just how do they perform better or how do they lose weight. Little bit of an explanation of ketosis, how you enter it, and also why you care about it at the levels where you’re doing research.

Dominic:      I got into this research because I was intensely looking into an anti-seizure strategy. I kind of exhausted all options and then I discovered that the ketogenic diet – I thought it was used primarily for weight loss – but I discovered the real function of the diet, how it came about, was for controlling drug resistant seizures, and it has roots back in the 1920s and earlier. That was essentially what I was being paid to do, to develop an anti-seizure strategy for oxygen toxicity which can happen while breathing a high oxygen with a special unit … Special ops guys use a closed-circuit rebreather and it can create seizures if they dive too deep.

The diet interested me; the evidence showed that it was probably better than most drugs out there, and obviously it didn’t have side effects associated with anti-seizure medication. I became interested in that but more importantly interested in how to mimic this with a ketogenic agent. The ones that were out there are like MCT oil, but I wanted to develop a ketone ester, which if taken orally can put you into starvation level ketosis in 15 minutes to a half hour and sustain it for hours.

In the process of developing that and testing that, we demonstrated that it has very strong anti-seizure effects and that ketosis has the broad range applications for neurological diseases and even cancer, we’re studying now. From a performance enhancement point of view, ketones function as an alternative fuel for your brain and for your muscles, too, so we are looking at the application of a ketogenic diet and also supplemental ketones to enhance cognitive performance and also physical performance.

Dave:             I’m working on some studies of my own given that I make MCT oil and some of the even more filtered versions like my Brain Octane stuff. I’m interested in the cognitive performance aspects of it so I’ve done some limited experiments with EEGs and it’s kind of amazing what mental endurance does when you have ketones in the body. Where can I get some of these ketones esters that you’re talking about? Sign me up.

Dominic:      They’re pretty new, actually – at least in our lab. The military has been working on these things for a while. Maybe the last ten years, but probably only in the last few years have they been able to be produced in a way that’s safe and that can be applied to humans. Ketone esters probably won’t be available for a while as a nutritional supplement. Maybe it’s a medical application. They taste horrible; stomaching them is really a hard thing. There is a product-

Dave:             The quote I’ve heard is that they take like ass, like worse than glutathione so far. Is that true?

Dominic:      Yeah, they do. There’s not a whole lot of people who have consumed them so I probably know the person you’re talking about, because there’s a very limited amount of people who have used these – maybe some advanced athletes and military guys.

Dave:             This [crosstalk 07:56 ] a connection.

Dominic:      Okay. Patrick Arnold, he’s a chemist, he has a company called Prototype Nutrition and he sells a product called KetoForce and that is kind of like a poor man’s version of a ketone ester I think and it’s essentially ketones that can be absorbed and rapidly assimilated and used for fuel. Our lab has found that that’s a very effective way to elevate ketones but it’s even more effective when it’s combined with MCT oil. We’re testing this right now and the application for this for cognitive function and performance is very real.

I think it would be best used in athletes that are already keto-adapted, meaning that their systems are already used to utilizing ketone bodies as an energy substrate. When we’re in a keto-adapted state the mechanisms for utilizing and transporting ketone bodies to muscles in the brain are up-regulated. I have a hunch just based on our research that a person wanting to enhance performance would be best suited to use this in combination with a low-carbohydrate diet.

Dave:             This has been an ongoing question.

Dominic:      I think I know-

Dave:             I use a lot of Brain Octane, which is the shorter chain MCT is extracted from plain MCT oil. I use both of them but I get a lot less of the GI problems when I use that, and I use it primarily for cognitive enhancement. I’m doing probably four tablespoons of that stuff a day, sometimes a little more, sometimes a little less. I can use ketones for energy all day long, I feel great, but I do eat carbs, probably 50 grams, sometimes 100 grams, and sometimes I go deep into ketosis. Am I going to be able to burn ketones and use those at the same time there’s some glucose in my body if I have an extra-normal amount of ketones because I’m taking all that oil?

Dominic:      Yes. Recently Joe LaManna, who’s a top ketogenic diet researcher, gave a talk here at the University of South Florida and his research has shown that ketones spare glucose in the brain. The brain will preferably use ketone bodies over glucose. I get this question a lot: are ketones the preferred source of energy for the brain? I get this question no less than 50 times, I think. I always said “Well, we don’t know that.” The emerging research that’s just starting to come out and will come out in the next year will demonstrate that ketone bodies are in essence a preferred fuel that the brain will use them in place of glucose and spare glucose.

We know from the work of Richard Veech and several others that ketones are very efficient metabolic fuel, probably more so than glucose. You have an alternative fuel that can potentially enhance metabolic efficiency and ATP production, and that can spare glucose. In part, the big advantage of the ketogenic diet is that when you’re following a ketogenic diet and you’re exercising, you can tap into your fat reserves and mobilize fat as a fuel source more efficiently and thereby preserving glycogen stores. The ultimate determining factor in how long you can go is the preservation of glycogen stores. Once they’re depleted you basically bonk. If you’re on a carbohydrate-restricted diet … Your diet sounds like it’s carbohydrate-restricted-

Dave:             It is.

Dominic:      50 to 100 grams is, yeah. You’re essentially in ketosis. You’re bounc