375 - The ketogenic diet, ketosis, and hyperbaric oxygen: weight loss, cognition, cancer, and more

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:11 – 5:40

   Dom & Peter’s shared interest in ketosis

   1. PAPeter Attia0:11

      Hey, Dom. Thank you for making the trip out to Austin. It's, uh... Boy, it has been a long time since we've been in person. I, I'm, I'm afraid to, uh, to hazard a guess as to when, but I know you and my brother see each other a lot more.

   2. DDDom D'Agostino0:24

      Yeah. [laughs]

   3. PAPeter Attia0:24

      And I'm always getting pictures of you visiting him and him visiting you.

   4. DDDom D'Agostino0:28

      Yeah, yeah. Paul's amazing. Yeah, he, uh, he's a mentor to me and, as you are, and through the health, and Paul's like an amazing, you know, entrepreneurial mentor and a life mentor in many different ways, so. But great to see you both. And, uh, you guys are such, you know, uber high achievers in different domains, and I think it's great to see, you know... It's great to see you in person for one thing, but it's great to see both of you thrive in doing what you do.

   5. PAPeter Attia0:53

      Well, the same can be said for you. Um, Dom, you've been on the podcast a couple of times, but I, I know that in podcast land, uh, it's, A, we've probably got, you know, hundreds of thousands of listeners today that weren't listeners, you know, the first and second time you were on the podcast. Um, and frankly, those that were, I think it would be understandable that they've forgotten most of what we've spoken about. Um, and maybe just by way of background, I'll, I'll let folks understand how, how you and I connected. I believe Ken Ford connected us back in 2011-ish, thereabouts. Um, at the time, I had-- was about a year into experimenting with a ketogenic diet, um, having all sorts of interesting success with it, for the most part, once I, once I got over the hump of figuring out how to do it. Um, and I think we must have connected at, uh, at his institute, and then the rest is kind of history. We, we then, through our friendship, became very, uh, deeply involved [laughs] in the testing of the earliest generations of, um, f- various forms of synthetic ketones, a topic we will undoubtedly get to today because it's impossible to imagine how much proliferation there has been of these things that were-

   6. DDDom D'Agostino2:08

      [laughs]

   7. PAPeter Attia2:08

      I mean, literally, you're sending me-

   8. DDDom D'Agostino2:10

      Yeah

   9. PAPeter Attia2:10

      ... like dirty plastic bottles-

   10. DDDom D'Agostino2:12

       Yeah. [laughs]

   11. PAPeter Attia2:12

       ... with stuff in my kitchen that I'm experimenting with, and, and it's like, now look at what you've done. Um, so m-maybe let's just talk a little bit about how your interest in this space came to be. So, um, for, for even for my recollection, I don't recall, your PhD was in neuroscience, if I'm not mistaken.

   12. DDDom D'Agostino2:29

       Yeah, uh, nutrition, and then at the time, studying nutrition and biology, I started doing, uh, a undergraduate thesis project in neuroscience and the neural control of autonomic regulation. So specifically the brain network, the rostral ventrolateral medulla. So they are the brain stem network that controls respiration. Uh, so inspiratory neurons, expiratory neurons, and how they respond to oxygen and, and, uh, CO2. And that led me down the path of oxygen hypoxia, hyperoxia, hypercapnia in extreme environments, and what, what happens to the brain under oxygen deprivation and nutrient deprivation. At the time, I was interested in alpha L-polylactate because it was in Cytomax, which was something I used because I raced mountain bikes. So [laughs] I was testing some things, uh, lactate, and then I got steered onto the ketogenic diet, uh, after getting a fellowship, a pr- a postdoctoral fellowship by the Office of Navy Research, which is part of the Department of Defense, to understand the cellular and molecular mechanisms of central nervous system oxygen toxicity, which manifests as seizures. So I was mostly interested in drugs, but then I pivoted and went back to the ketogenic diet because the ketogenic diet works for many different seizure disorders when drugs fail. So I was like, "Oh, I can get nutrition back." Although I was gravitating towards a tenure track position and everybody told me, "This is like the dumbest thing to do to like... You're, you can't get NIH funding with, you know, ketogenic... Nobody heard of the ketogenic diet back then."

   13. PAPeter Attia4:02

       What year was this?

   14. DDDom D'Agostino4:03

       Uh, this was around 2005. I started tinkering with ketones, but 2007 I started writing grants, and then I hit on a grant in 2008, like postdoctoral, uh, grant. And I was at a weird position from postdoc to something called a research assistant professor, which is like an intermediate position before you get into a tenure track, and the university was just kind of gauging to see my productivity. And, uh, as my postdoctoral grant was very sizable, it was above like an NIH level grant, which I was-- and it paid full indirects for that. And we can talk about, you know-

   15. PAPeter Attia4:35

       And that, that came from the military?

   16. DDDom D'Agostino4:37

       Yeah. Office of Navy Research is part of the Department of Defense. And then, uh, and then I got good data on hyperbaric atomic force microscopy, very mechanistic research. I also did patch clamp electrophysiology and confocal microscopy. Uh, my work was really focused on redox mechanisms and looking at superoxide production under graded levels of oxygen and different, different metabolites. So in the process of doing all that, I had no interest in cancer, but we had some glioblastoma cells, and we threw them into the hyperbaric chamber, and under, uh, under confocal microscopy, we could see the mitochondria were lighting up and then kind of exploding or disappearing, uh, in the cancer cells, and that was kind of unique. And, uh, and that led me on a side tangent thing to study cancer. But my central thing that I studied was neuroscience, and I've always-- I've been in a neuroscience department and just mainly focused on that.

   17. PAPeter Attia5:37

       Let's go back to something you said at the outset, just 'cause folks might not understand

3. 5:40 – 14:20

   Dom’s work for the Navy on oxygen toxicity

   1. PAPeter Attia5:40

      why the Navy would be interested in the effects of too much oxygen, right? When you think of the Navy, you think of being underwater. When you think of being underwater, you think of oxygen deprivation. So what is it about certain types of diving that actually bring about the opposite problem?

   2. DDDom D'Agostino5:57

      Yeah, good question. Uh, so hyperbaric oxygen, you experience that with hyperbaric oxygen therapy, right? And there's fourteen different FDA-approved applications, and the you-- in that context, you only go to about a maximum of two point five to three atmospheres of pure oxygen. In the context of military diving, like a Navy SEAL use a closed circuit rebreather because there's no bubbles, so there's a stealth component to that, and you're breathing, uh, high concentrations of oxygen, and at, at 50 feet of seawater, the potential for oxygen toxicity exists. Uh, in just 10 minutes-

   3. PAPeter Attia6:34

      And just explain to folks-- Sorry, Dom.

   4. DDDom D'Agostino6:35

      Yeah.

   5. PAPeter Attia6:35

      Explain to folks exactly what that is.

   6. DDDom D'Agostino6:37

      Yeah.

   7. PAPeter Attia6:37

      So how does a rebreather work?

   8. DDDom D'Agostino6:39

      Mm-hmm.

   9. PAPeter Attia6:39

      What's the concentration of oxygen that they're breathing in?

   10. DDDom D'Agostino6:42

       Yep. So, uh, a closed circuit rebreather, for example, like a Dräger rebreather, like the original ones, uh, those early rebreathers, and even now, it's high concentration. It's like a h- essentially 100% oxygen, right? You're breathing 100% oxygen. So there's no nitrogen. There's 80% nitrogen air-

   11. PAPeter Attia7:00

       Yeah

   12. DDDom D'Agostino7:00

       ... we're breathing right now, right? Uh, there's no nitrogen, so you avert the potential for nitrogen narcosis. So nitrogen's not narcotic at one atmosphere, but there you get something called the Martini effect, and as you go down lower, nitrogen becomes narcotic. So that's something else that we study. But, uh, so you're breathing 100% oxygen, and, uh, and then there's a CO2 scrubber. So you're blowing out the exhaled carbon dioxide is scrubbed out from the breather, and, uh, and that keep-- It's a closed circuit, so there's no off-gassing associated with, uh, scuba diving or even other types of, uh, technical diving where you have some off-gassing, right?

   13. PAPeter Attia7:39

       And the reason that they can do that is because you're not wasting gas on the 80% nitrogen. You basically, you're, you basically just have to store the CO2 that's coming out once you've scrubbed it. You've got pure O2 coming in, so your tidal, your, your volume of air needed is much lower 'cause you're just solving for the oxygen?

   14. DDDom D'Agostino7:57

       That's part of it because the oxygen tanks are, are pretty small, right, with a rebreather. But, uh, uh, it's analogous to, uh, we have a couple ponds on our property, right? And I, I, uh, when I go in the pond and, uh, and I see bubbles coming across the pond, I know an alligator is coming towards me, right? So that's how I... When your brother was there, we were like, [chuckles] we were looking at the alligators and, and just, uh, getting them to come to us by throwing pebbles in there when they hear something. So if I go to the lawn, to the pond with a weed whacker, I see bubbles coming across. So analogous situation would be a Navy SEAL coming across a body of water that's still. You can clearly see the bubble trail coming to you. So with a, a closed circuit rebreather, that completely averts that, the bubble trail, and then there's also the noise that the bubbles make, right? So you don't have that. The problem is if you're wearing a closed circuit and you dive down to 100 f- like 100 feet of seawater because someone starts shooting at you or you have to go down deep to put a mine on the bottom of a bridge or something like that, you're gonna have a seizure within, like, five minutes. So oxygen is a stimulant.

   15. PAPeter Attia9:02

       Hmm.

   16. DDDom D'Agostino9:02

       It stimulates a massive amount of, uh, glutamate release that activates AMPA receptors, NMDA receptors. Uh, it stimulates the neural network, um, in ways. It also sort of deactivates or inhibits an enzyme, glutamic acid decarboxylase, which converts more glutamate to GABA. So there's like, uh, a s-- and there's a big burst in reactive oxygen species. So you have a constellation of things going on in your brain. So I study the negative effects of high, high oxygen, which kind of has some people who study hyperbaric oxygen a little bit standoffish towards me [chuckles] 'cause I study the ne-- But in the context of lower oxygen, oxygen, uh, hyperbaric oxygen therapy can be very therapeutic, and we can talk about that too.

   17. PAPeter Attia9:44

       Well, I, I do want to talk about that-

   18. DDDom D'Agostino9:45

       Yeah

   19. PAPeter Attia9:45

       ... Dom. So, um, there's a lot I want to ask you about hyperbaric oxygen, but I want to finish the swing on this-

   20. DDDom D'Agostino9:51

       Mm-hmm

   21. PAPeter Attia9:51

       ... particular application. When was it clear to the Navy the problem that you describe, which is when we have, um, closed circuit rebreathers with 100% oxygen, we're running into problems with our divers, and it-- These problems are dramatic. I mean, if you have a seizure at 100 feet, you're gonna die pretty quickly. So h- when, when did they come to realize this and, and-

   22. DDDom D'Agostino10:13

       [laughs]

   23. PAPeter Attia10:14

       How-- Is this, is this-

   24. DDDom D'Agostino10:15

       Yeah

   25. PAPeter Attia10:15

       ... was this a relatively recent discovery?

   26. DDDom D'Agostino10:17

       No, it's not. And my mentor, Dr. Jay Dean, uh, our lab is like a museum, so we have all the historic pictures on there.

   27. PAPeter Attia10:24

       Hmm.

   28. DDDom D'Agostino10:24

       And there's a guy that wrote a book, and his name was Fred Bear, and, uh, he was a, a French physiologist. And, uh, he did a lot of seminal studies back, you know, over, well over 100 years ago in the 1800s, showing that, like, you could give animals-- Uh, they called it, like, uh, caissons disease too, so that could-- But when you go down in, like, chambers when you're building a bridge, you're under high pressure oxygen or, or high atmospheric, uh, effects. So yeah, I would say about 150 years ago-

   29. PAPeter Attia10:55

       [laughs]

   30. DDDom D'Agostino10:55

       ... we realized that oxygen was a stimulant. We didn't know why. And, uh, and then with military diving, then you have the problem of, you know, averting oxygen seizures. And there's a number of people in the Navy, Frank Butler comes to mind, Claude Pianadosi, Richard Moon. There's, there's, uh, a network at Duke University which did a lot of the seminal studies. And, uh, and that of-- And they established the dive tables for preventing oxygen toxicity seizures, nitrogen narcosis, high pressure nervous syndrome. So these are all things that you have to avert, like, when you're diving, depending on what kind of diving you're doing.
4. 14:20 – 18:58

   Nutritional ketosis defined & how fasting & diet generate therapeutic ketones

   1. PAPeter Attia14:20

      I'm going to come back and talk about a lot of these things, but I feel like we should now kind of get people up to speed on what ketones are. Again, we-

   2. DDDom D'Agostino14:27

      Yeah, sure.

   3. PAPeter Attia14:27

      We can sit here and talk about this and take this stuff for granted all day. You obviously threw around the term nutritional ketosis. You've also talked about supplemental ketosis, sometimes referred to as exogenous ketones. Let's start with nutritional ketosis and just give people, um, some definitions of, um, how you achieve it, how much variability there can be in a diet to get there, what the thresholds are, and a little bit about what's happening physiologically.

   4. DDDom D'Agostino14:52

      Yeah. Uh, before I, before I begin, I want to direct people to your early blogs, which I assume are still up [chuckles] on nutritional ketosis.

   5. PAPeter Attia14:59

      I, I-- I'm sure they are somewhere, yeah.

   6. DDDom D'Agostino15:01

      Yeah, on the delta G. There's one with exogenous ketones, you know. In our study, we kind of did with, uh, the ketone salts-

   7. PAPeter Attia15:07

      Yep

   8. DDDom D'Agostino15:07

      ... which increased your, uh, efficiency, oxygen utilization. So nutritional ketosis, uh, the key to... Well, let's take a little bit of a step back. Ketosis, uh, I like to start with fasting. So when you stop eating, right, you suppress the hormone insulin. You mobilize fatty acids for fuel. The brain's not a good-- It can't use the long-chain fatty acids that are stored in your adipose tissue. So through beta-oxidation of fatty acids in the liver, uh, beta oxy-- accelerated beta-oxidation in the context of insulin suppression generates these molecules, beta-hydroxybutyrate and acetoacetate. And then they spill into circulation, and, uh, they become largely responsible for preserving brain energy metabolism in the context of, uh, energy deprivation or carbohydrate restriction. So-- And the elevation of beta-hydroxybutyrate or acetoacetate in the blood, in the urine, or the breath becomes a biomarker, so, uh, for k-ketosis. So you can achieve ketosis through fasting, through diet, through supplements, or, uh, alcoholic ketoacidosis, right? That's another thing, or diabetic ketoacidosis, and we could talk about that in context. And then you have nutritional ketosis, which is eating carbohydrate-restricted ketogenic diet that's primarily high in fat. The original diet was ninety percent fat. Modified versions of the diet are about sixty to seventy percent, uh, fat with higher protein. Now we know, especially in kids, if you restrict protein too much, you could stunt their growth and have some issues there. So clinically, a modified version of the ketogenic diet is actually being kind of gravitated more towards even in pediatric epilepsy. So we're learning that protein is really important, and it was underappreciated, I guess, in the early ketogenic diets. In the context of sports, it's extremely important, and we can talk about that. So but still, it remains that, uh, the ketogenic diet is the most scientifically researched diet that has an objective biomarker that defines the physiological state of being in the diet, and that's, uh, beta-hydroxybutyrate above zero point five millimoles per liter. So that's clinical ketosis. And in the context of ketosis, it has, um, uh, there are remarkable changes in our metabolic physiology and the neuropharmacology of our brain, and also beta-hydroxybutyrate has very unique effects, uh, epigenetic effects, which is kind of a new buzzword that people are talking about, and we, we, uh, my student just finished a project on that. Um, and I think there's, uh... it's pleiotropic. So ketogenic diets have pleiotropic effects, and, uh-

   9. PAPeter Attia17:48

      Tell folks what that means.

   10. DDDom D'Agostino17:49

       Yeah. Pleiotropic is kind of like a fancy, somewhat nebulous word that basically means there are multiple mechanisms that are activated, um, biochemically, physiologically, neuropharmacologically, uh, that have beneficial effects. So, um, and I can go through the explosion of research that has occurred on PubMed and clinicaltrials.gov. But the important thing is that, uh, nutritional ketosis or therapeutic ketosis, uh... or let's take a step back. The ketogenic diet, some people say the ketogenic diet is not magical. The ket-- it does nothing magical. In the context of body composition alterations or fat loss, that could be-- there's truth to that. However, I, I, I say there's a hard stop there. The ketogenic diet is indeed a magical diet in the way that, uh, it remarkably changes our physiology and there's no other diet, uh, that exists that can, for example, manage drug-resistant seizures, and it does that because it profoundly changes our fuel system, our physiology, our biochemistry, and our neuropharmacology.

5. 18:58 – 25:08

   History of ketogenic diets for epilepsy, & evidence showing ketones reduce seizure activity & strengthen brain resilience

   1. PAPeter Attia18:58

      But let's talk a little bit about that. You've mentioned-

   2. DDDom D'Agostino18:59

      Yeah

   3. PAPeter Attia18:59

      ... it a few times now. Um, so let's help folks understand what's going on here. So y- this was first, um, identified in kids, and if I'm not mistaken, um-

   4. DDDom D'Agostino19:10

      Well, adults actually, if you go back to-

   5. PAPeter Attia19:11

      Oh, is it adults?

   6. DDDom D'Agostino19:12

      Yeah, like the Mayo-

   7. PAPeter Attia19:12

      Okay

   8. DDDom D'Agostino19:12

      ... Clinic in 1920s because there was no drugs-

   9. PAPeter Attia19:15

      Got it

   10. DDDom D'Agostino19:15

       ... for epilepsy. So we g-

   11. PAPeter Attia19:17

       So what gave them the idea-

   12. DDDom D'Agostino19:18

       We defaulted. Uh-

   13. PAPeter Attia19:19

       ... that, "Hey, we've got these-

   14. DDDom D'Agostino19:20

       Mm-hmm

   15. PAPeter Attia19:20

       ... people that are experiencing this awful thing." Now, they had EEGs back then, but they really didn't know much.

   16. DDDom D'Agostino19:25

       True, yeah. Yeah, they actually did some really good physiology back in the 1930s and '40s. Underappreciated.

   17. PAPeter Attia19:30

       Yeah.

   18. DDDom D'Agostino19:30

       Uh, well, we knew that fasting controlled seizures, right? I mean, like ancient literature-

   19. PAPeter Attia19:35

       So that was the first observation.

   20. DDDom D'Agostino19:36

       Yeah, I mean-

   21. PAPeter Attia19:36

       Okay

   22. DDDom D'Agostino19:36

       ... the Gospel of Mark talks about, you know, fasting. I mean, there's ... It, it's all over, like, in the literature.

   23. PAPeter Attia19:41

       Interesting.

   24. DDDom D'Agostino19:41

       Fasting could control seizures. So a ketogenic diet by virtue of elevating these ketone bodies, which were showing up in the blood and the urine and even in the breath, uh, they just understood that these ketone bodies were somehow associated with seizure control, and we did not have anti-seizure drugs back then. So-

   25. PAPeter Attia19:57

       And when were these first identified? So, so you've got-

   26. DDDom D'Agostino20:00

       Mm-hmm

   27. PAPeter Attia20:00

       ... Banting and Best identify insulin or at least isolate-

   28. DDDom D'Agostino20:03

       Yeah, yeah

   29. PAPeter Attia20:03

       ... insulin in the 1920s.

   30. DDDom D'Agostino20:04

       Yes, uh-huh.
6. 25:08 – 33:05

   Dom’s personal experience on the ketogenic diet: tracking macros, protein, & ketone levels

   1. PAPeter Attia25:08

      You've obviously experimented a lot with the ketogenic diet yourself. I mean, when did you first try a ketogenic diet?

   2. DDDom D'Agostino25:14

      Like the clinical ketogenic diet where I got the little CardioChek meter, which was super expensive at the time, I would say 2009 I started actually checking ketones. And, uh, and the Cardio-- they still have th- this CardioChek meter.

   3. PAPeter Attia25:28

      I was using the Abbott one.

   4. DDDom D'Agostino25:30

      Yeah.

   5. PAPeter Attia25:30

      Precision Xtra.

   6. DDDom D'Agostino25:31

      Abbott, the Precision, I got that later. I don't even think that might have been out yet, [laughs] but I got that soon after because the CardioChek actually did like your HDL and like triglycerides-

   7. PAPeter Attia25:41

      Yeah

   8. DDDom D'Agostino25:41

      ... and things. It was a little bit... We compared it to, uh, we also had like an, a lab assay, like an ELIZA assay-

   9. PAPeter Attia25:47

      Yep

   10. DDDom D'Agostino25:47

       ... so yeah, we were comparing it to. Uh, yeah, and then we got, um, the, the Precision Xtra by Abbott. And then I remember I bought something like 10-

   11. PAPeter Attia25:55

       Back then the strips

   12. DDDom D'Agostino25:56

       ... $10,000 of strips.

   13. PAPeter Attia25:57

       I was about to say-

   14. DDDom D'Agostino25:57

       Yeah [laughs]

   15. PAPeter Attia25:57

       ... the strips were $5 to $10 each-

   16. DDDom D'Agostino26:00

       Yes

   17. PAPeter Attia26:01

       ... at the time.

   18. DDDom D'Agostino26:02

       I found, uh, I bought them in bulk and I think-

   19. PAPeter Attia26:05

       Yeah, you hooked me up at one point-

   20. DDDom D'Agostino26:06

       Yeah

   21. PAPeter Attia26:06

       ... and you were able to get them for like $1.50 or something.

   22. DDDom D'Agostino26:09

       Yeah. Bought like-

   23. PAPeter Attia26:09

       But I was going through-

   24. DDDom D'Agostino26:10

       ... 10,000 strips

   25. PAPeter Attia26:10

       ... three a day.

   26. DDDom D'Agostino26:11

       Yeah. Oh, yeah.

   27. PAPeter Attia26:12

       At least you still, yeah.

   28. DDDom D'Agostino26:13

       Yeah, so, uh, that price point has come down, but now we have the Keto-Mojo, which is actually, uh, aligns more with our assays and, uh, and it does the glucose ketone index that we can talk about. Uh, yeah, so I started doing that and I have to-- when I started it, within, I guess, five years after starting the ketogenic diet, I probably rapidly lost 10 to 15 pounds. And then my, my exercise and my lifts tanked too. Like, I lost strength on bench press and not so much deadlift and squat, but I saw that, but I didn't really care that much at the time. But I also learned the lesson that protein was really important. I was thinking ketones would be basically save, you know, muscle and, but it- they don't. They have an anti-catabolic effect that we can talk about, but there's nothing, you know... When, if your protein goes from like 250 grams a day to like, you know, 70 to 80 grams per day [laughs] , you're gonna lose a lot of muscle, and the ketones have a sparing effect.

   29. PAPeter Attia27:05

       Just don't tell the USDA that or, you know-

   30. DDDom D'Agostino27:07

       Yeah
7. 33:05 – 41:02

   Using a ketogenic diet for weight loss: guidance on protein, fiber, calorie tracking, lipid monitoring

   1. PAPeter Attia33:05

      So if mistake number one is you're not measuring your actual ketone levels and you're not tracking what you're eating, so you can see the association of, "Hey, when I ate this, it went down. When I ate this, it went up." Um, what are some other mistakes people make with their diet formulation? Is it too-- Is, is, is... Are they typically erring on the side of too much protein, not enough protein? Are they not realizing where carbs are sneaking into their diet? And-

   2. DDDom D'Agostino33:27

      Yeah

   3. PAPeter Attia33:27

      ... and what kind of guidance do you give people? How many grams of carbs a day do you tell somebody, or do you vary that based on their activity level?

   4. DDDom D'Agostino33:33

      Yeah. Taking a step back. So I view, unlike many people out there, I view a ketogenic diet as a prescription metabolic therapy. [laughs] So that's the world that I come from.

   5. PAPeter Attia33:45

      Yeah.

   6. DDDom D'Agostino33:46

      You know, and then there's like, you know, there's clinical keto and then there's, like, internet keto. So a, a... In which a lot of people are following a low carb diet, which has a plethora of m- metabolic benefits. You know, you just have to be up on your blood work, and you have to be very vigilant with tracking, you know, your biomarkers. Uh, but a clinical ketogenic diet is typically done, uh, with consulting or advice or even following the framework of, for example, a lot of books out there by Eric Kossoff. Uh, if you have cancer, Merriam Kalimian has a guide, Ketogenic Diet for Cancer. Uh, so books that are out there that tell you step by step on how to do it. And from a practical or logistical point of view, w- we had a, a small study we ran with Dr. Allison Hall, uh, that looked at people that were just, uh, they didn't have any overt pathology, but they were just like, take normal people, put them on a low carb ketogenic diet. And over-- The practitioners tell me that if you transition a person over four to six weeks, they adhere to it better, and you actually get more favorable health responses. You don't have a lot of funky blood work that come back. You know, it could be the electrolytes. With people that have certain mutations with fatty acid oxidation disorders, even ApoE4 carriers tend to... Like, you'll see their LDL go up, and you'll see things like HDL go down, and you'll see they start the diet and their triglycerides go up. Like I, you know, I've seen that a lot in quite a few people, and I think there's some genetics that need to be unpacked there. Uh, in several cases it was people that were ApoE4 carriers, like they were homozygous. So I think there's something to unpack there. They just don't, uh, metabolize... Their lipid metabolism is a little bit different. So I think it's really important to get blood work, track triglycerides, track HDL, ApoB, LDL, hemoglobin A1C, insulin levels, I think. I've seen people's insulins go up, but generally speaking, 90% or 80% or more insulin goes down. Uh, but really just to, um, to use, there's so many different guides out there, and if you're doing it to manage a clinical condition, you should be working with a registered dietitian that's savvy. And the people I recommend, there's Advanced Ketogenic Therapies, and it's a team of people, and it's kind of spearheaded by, uh, Denise Potter. She's a registered dietitian, but she was-- came from the world of epilepsy and worked as a conventional registered dietitian and then transitioned to ketogenic and now has a team of a half dozen or more people.

   7. PAPeter Attia36:18

      But if someone just says-

   8. DDDom D'Agostino36:19

      Yeah

   9. PAPeter Attia36:19

      ... "Look, I just want to do this on my own, just like any other-

   10. DDDom D'Agostino36:21

       Yeah

   11. PAPeter Attia36:21

       ... diet I might follow," what would be sort of the guidance you'd give them?

   12. DDDom D'Agostino36:24

       Yeah, it depends, you know, why they want to use it. Uh, many, most people-

   13. PAPeter Attia36:26

       Well, I think the most common reason would be weight loss, right?

   14. DDDom D'Agostino36:28

       Yeah, weight loss. Uh, so I would say calories are super important, so just, uh, gravitate towards a high protein ketogenic diet. And if it's just purely weight loss, I would say high protein, moderate fat, and then high fiber. So the carbohydrates that you're getting, uh, should be just fibrous carbohydrates. So you can get 50 to even 100 grams of carbs per day if one third of those carbohydrates are fiber. So that excludes all ultra-processed food, even processed food. Like broccoli is about one third fiber. So if you go down the list, there's about... I think I have a list of about 30 or 40 forms of carbohydrates that are about, like, one third, uh, a quarter to one third fiber. So if you're pulling from that list, uh, you're gonna have-

   15. PAPeter Attia37:15

       So you've got, you've got all your leafy vegetables.

   16. DDDom D'Agostino37:18

       Yeah.

   17. PAPeter Attia37:19

       You mentioned broccoli. Would carrots be in there?

   18. DDDom D'Agostino37:21

       No, no. Broccoli, cauliflower. Uh, carrots, no, especially if they're cooked, they're high-- they can be highly glycemic.

   19. PAPeter Attia37:27

       Mm-hmm.

   20. DDDom D'Agostino37:27

       Uh, but avocado

   21. PAPeter Attia37:29

       Bell peppers?

   22. DDDom D'Agostino37:30

       Yeah. Bell peppers are a little bit too high in sugar. They're at the cutoff point. Maybe like a green pepper or something like that. But generally things that you'd find in like, you know-

   23. PAPeter Attia37:39

       Cucumber?

   24. DDDom D'Agostino37:40

       Cucumber, yes. Um, you know, uh, asparagus-

   25. PAPeter Attia37:45

       Tomato?

   26. DDDom D'Agostino37:45

       ... is-- Tomato, no. Tomato's like a fruit, pretty high in sugar. So these are things that you need to be kind of vigilant. And there's a lot of, you know, go-to guides. And that's why I think it's important to use like a tracking app, right? And you don't have to do it-- Like, I would never use... Oh, I use it now time to time if I want to make adjustments, so, um, and, and be very vi- 'cause one thing I noticed, especially using the Carbon app or other apps, is that I was like, "Eh, I'm getting about three, 3,200 grams of, of... or 3,200 calories per day." But when I put it into these tracking apps, it's more like 4,000 calories per day. I, you know, uh, always-

   27. PAPeter Attia38:21

       Meaning you think you're at 3,200

   28. DDDom D'Agostino38:22

       ... underestimate it.

   29. PAPeter Attia38:23

       Yeah.

   30. DDDom D'Agostino38:23

       Yeah. I always, always underestimate it, uh, probably because just fat is so calorically dense, right? So the amount of egg yolks and a lot of fatty fish. This morning I had like three cans of sardines. Each can is 20 grams of fat and 15 grams of protein, and that's... So 20, that's 60 grams of fat just from sardines and extra virgin olive oil, [laughs] you know. And that's, uh, it adds up. It just seems like, oh, this is like nothing. This is like, you know, it's less than I would have if I'm eating at home. But, uh, it adds up. And I think that people that are not losing weight or managing whatever they're trying to manage with a ketogenic diet, they need to track calories. And simple cal- caloric restriction or creating even like a 10% or 20% energy deficit will be the big lever that's gonna cure 90% of what most people are seeking the ketogenic diet for. And you could do that with a standard diet.
8. 41:02 – 44:56

   Protein on ketogenic diets: rationale for higher intake

   1. PAPeter Attia41:02

      when I stop eating carbohydrates and ramp up my fat... Uh, by the way, I do wanna go back to, sorry, one other point. You keep saying high protein. Can you define high protein in this context? You talk, I mean, are you talking high by the standards of the RDA, or are you just saying like, you know, are you saying like one gram per pound of body weight? Is that sort of your guidance?

   2. DDDom D'Agostino41:22

      Yeah, I mean, historically, you know, 8 to 10 to 12% [laughs] was used with ketogenic diets, so I'm talking about a ketogenic diet that's 20% to 30% protein. So that's considered high by-

   3. PAPeter Attia41:36

      But that's hard for people I think sometimes. I mean, you can obviously back calculate into that-

   4. DDDom D'Agostino41:40

      Yeah. Mm-hmm

   5. PAPeter Attia41:40

      ... by the calories. But do you-

   6. DDDom D'Agostino41:41

      Yeah

   7. PAPeter Attia41:41

      ... find it easier to just say, "Look, keep your carbs at 50 grams and try to-

   8. DDDom D'Agostino41:46

      Mm-hmm

   9. PAPeter Attia41:46

      ... get them from high fiber carbs, get your protein to X grams, and then limit your total calories to, whatever, 3,000 with fat filling the rest"? Um, in other words, what is it typically working out to in terms of grams per pound of body weight in term, in protein?

   10. DDDom D'Agostino42:03

       Mm-hmm. Yeah, in protein. Uh, I, if me for example, right? So, uh, would be upwards of, I'm about 220 pounds, so that would be, uh, I know it sounds crazy, but you know, from the average RD, [laughs] registered dietician, but 220 grams of protein.

   11. PAPeter Attia42:20

       Yeah.

   12. DDDom D'Agostino42:20

       So that would be the upper end if I'm very active and-

   13. PAPeter Attia42:23

       Yep

   14. DDDom D'Agostino42:23

       ... I mean, today, maybe I won't get that or when I'm traveling. But that amount of protein I think, uh, is the upper end. I don't think there's any benefits to go above and beyond, beyond that.

   15. PAPeter Attia42:33

       And at that level of protein, you're not undergoing so much gluconeogenesis that you're making too much glucose that's offsetting the ketone process?

   16. DDDom D'Agostino42:41

       Yeah. Everybody's a unique, uh, metabolic entity, so they're gonna have a different response. But for me personally, uh, especially having eaten 400 or 500 grams of protein, and that's not, I'm not exaggerating there, when I was in my late teens and 20s, uh, that works for me. That level of protein works for me. Uh, for some people, especially if they're going to jump from 50 grams a day or the RDA recommendations to, uh... And you want to do that to ideal body weight. So if you have someone that's-

   17. PAPeter Attia43:07

       'Cause the RDA for you is 80 grams

   18. DDDom D'Agostino43:11

       Yeah. Yeah.

   19. PAPeter Attia43:11

       Exactly 80 grams.

   20. DDDom D'Agostino43:12

       That's right. Yep.

   21. PAPeter Attia43:13

       You're, you're 100 kilos.

   22. DDDom D'Agostino43:14

       Yeah.

   23. PAPeter Attia43:14

       The RDA recommends you have 80 grams of protein, not 220 grams.

   24. DDDom D'Agostino43:19

       Yeah.

   25. PAPeter Attia43:19

       At 80 grams, you would not be able to maintain your muscle.

   26. DDDom D'Agostino43:22

       No, not in, not in my context, no, definitely not. Uh, the more muscle you have, the more protein... They're, they just have much higher protein turnover, so you're breaking down protein, building protein. That whole cascade is amped up probably several times higher in the co- especially if you're working out and breaking down protein and you have a fast metabolism. Uh, my recent, uh, you know, resting metabolic rate showed it was 34% higher, so I don't... You know, I don't know, give... I, I'd have to do further studies, but they thought it wa-... They wanted to redo it, and then they redid it.

   27. PAPeter Attia43:55

       That's even when adjusted for your lean mass?

   28. DDDom D'Agostino43:57

       Yeah, my resting, yep. So, uh, and I don't know. You know, I'm, I'm gonna redo it in about two weeks. I was also off creatine and some other things. I'm reloading on creatine, just started, and, uh, and gonna redo that again. But yeah, my, my lean mass is kind of... I'm pretty heavier, so I don't wanna throw... That's the upper limit, and I think if people... You can gradually increase your protein. But, um, pro- I've been very vigilant now with my protein, especially after turning 50, that this is important because things start to... Your sarcopenia and the loss of lean body mass is almost considerably higher, you know, as you know, like, in your 50s, and there's different reasons for that, but activity is the main mitigator for that. So if you're providing a stimulus for your body to grow and maintain muscle, you need, uh, protein that's double [laughs] the recommended daily allowance, I think, if you're really going to be proactive about it.

9. 44:56 – 48:21

   Incorporating carbohydrates into keto

   1. PAPeter Attia44:56

      Any other kind of quick dos and don'ts around things like fruit, berries, uh, artificial sweeteners?

   2. DDDom D'Agostino45:03

      Mm-hmm.

   3. PAPeter Attia45:03

      How do you think about all of those things as they factor into a ketogenic diet?

   4. DDDom D'Agostino45:07

      Yeah. Uh, I think fat and... I tend to, like, I guess, carb backload at the end of the day. I eat no carbs all day, and at dinner I'll have, like, a salad or vegetables. And then in evening I have wild blueberries, which have, like, a third of the f- the sugar of regular, uh, raspberries, blueberries, wild ones. And then I have, like, a, a keto mousse, which is just cocoa powder, chocolate ketone powder, and, uh, and some stevia or monk fruit and cinnamon in that, and it's, it has no effect on my CGM. It actually goes down. So, uh, I, I found out what works for me, and as long as I am eating, you know, fiber, if the p- if the carbohydrates are delivered with fiber, there's really no, uh, no glycemic, you know, counter effect to that, no spiking. Uh, I have a short list of foods. So it's basically, you know, berries, broccoli, asparagus, dark chocolate. Like, these are things that I eat every day. You know, maybe not the asparagus, but broccoli, berries, dark chocolate, uh, and salads. And, you know, that's enough. I'm kind of simple, and I keep things, you know, pretty simple. I don't, like, even have... In the past, I had a desire to have more different kinds of foods. Uh, I enjoy that. I mean, we were traveling in Greece, and I'm not going to, you know, pass up all the great food, like, when I'm traveling. Um, and I ate as much carbohydrates, you know, as whatever they were serving me, and I came back six pounds lighter because, you know, I'm in and out of the water every day. I'm walking out in the sun and things like that. So actually increasing, tripling, or quadrupling my carbohydrate made me lose six pounds when I come back, and I was... I thought for sure I was eating... I know for- I know-

   5. PAPeter Attia46:54

      But, but how did you feel? Did you feel different?

   6. DDDom D'Agostino46:56

      I felt, I felt great. Yeah. I'm pretty metabolically flexible, so I think that's also a consideration that if you really delve to, into carbohydrate restriction and your body is completely fat adapted and it's like carbohydrates are a foreign substance and glucose spikes are [laughs] ... You're going to have, uh, sort of a, a, a pretty big counterregulatory effect once you start getting, bolusing carbohydrates again. So because you're changing your physiology, you're changing enzymes, so your gut, for one thing, is not going to tolerate that. You know, and just from, like, fitness competitors, when they diet and then they finish the competition and then they go out and have, you know, like, a cheat meal, then they're up all night with gas and bloating because simply if you start-

   7. PAPeter Attia47:39

      Yeah

   8. DDDom D'Agostino47:39

      ... with... I mean, I could go through all the different systems, but the GI system takes a big hit. The liver takes a big hit. The glucose hitting the peripheral system can't absorb it, so your CGM goes off the charts, and that can trigger inflammation. That can alter, like, gut microbiome. It's going to affect your mood. Like, these are wild swings that yo-yo dieters go through. So if you're low carb and you achieve your goals, like your weight, and you want to... And you, you miss carbohydrates, you can slightly just titrate them back in and just, um, just do fibrous vegetables. Just start with that. And some people can't tolerate that. But, you know, low, uh, fruits, most people who have, like, an aversion to plants or some immune reaction to them usually can tolerate fruits.

   9. PAPeter Attia48:20

      So before

10. 48:21 – 53:10

    The carnivore diet

    1. PAPeter Attia48:21

       we go to the exogenous or synthetic ketones, I want to now ask you about an even more, uh, extreme form of diet, which I'm sure you get asked a lot about. I know I do, and I have no insight clinically, uh, nor do I have any personal experience with this. Let's, let's talk about this carnivore diet.

    2. DDDom D'Agostino48:35

       Mm-hmm.

    3. PAPeter Attia48:35

       So I don't... I, I realize there are different ways people go about doing this. There are some versions that are incredibly strict, where you literally are just eating meat and nothing but meat, and then there are others where you expand that into, well, you can eat other animal products. You can eat eggs. You can have dairy and things like that. Um, but let's start with just the meat only version of that diet. Now, first of all, w- what do you think is happening metabolically? How does one achieve ketosis with just meat? Because even the fattest serving of meat, even if you were eating just ribeyes, I don't imagine Well, I, I suppose it's possible that you could get 30% of your calories from protein and 70% from fat. So y- does it, does it produce a, a ketotic state as well typically?

    4. DDDom D'Agostino49:28

       I had a rib eye the other night I think would hit the keto macros because [laughs] it was a lot of fat, and I was kind of annoyed 'cause, you know, there was, like, less meat and more fat. But, um, yeah, I, I think you can achieve ketosis with a, a fatty carnivore diet, especially if calories are restricted.

    5. PAPeter Attia49:44

       But you couldn't do it if it was a New York strip or a filet. You just don't have enough fat in it relative to the protein, right?

    6. DDDom D'Agostino49:49

       Uh, you could if you were in a caloric deficit. So if you're in an energy deficit, right?

    7. PAPeter Attia49:55

       Yeah, fair point.

    8. DDDom D'Agostino49:56

       So your insulin's gonna go... Like, everything's gonna get... kinda go in the right direction, so. And that's the issue. Uh, I am a firm believer that, uh, carnivore diets can be therapeutic for people who have autoimmune disorders, so that's pretty clear.

    9. PAPeter Attia50:10

       Mm-hmm.

    10. DDDom D'Agostino50:10

        There's some people who, uh, they could also follow a path and do an elimination diet, but the carnivore diet is the ultimate elimination diet. So you're meeting your protein requirements, you're have enough protein to build muscle. Uh, protein has pretty much... Or c- you know, um, steak and an animal-based protein diet has pretty much all the micronutrients. I mean, you could argue, you could argue maybe, uh, vitamin C and magnesium, but you do not see vitamin C deficiency in people that are on carnivore diets, surprisingly. So there's some vitamin C in, like, liver and stuff, too. So if you're eating nose to tail, that's not something you have to worry about.

    11. PAPeter Attia50:48

        Yeah.

    12. DDDom D'Agostino50:49

        I've seen magnesium trending low, although we don't have the best magnesium, you know, measurements, but, uh, or the blood work for that. But I've seen, uh, magnesium being beneficial for people 'cause magnesium is something, it's... You, we get it from chlorophyll, right? It's like the central molecule of the, of chlorophyll, right? Magnesium. Uh, and we're not getting any of that really with a ketogenic diet or very little. So that's something-

    13. PAPeter Attia51:12

        I mean, you're getting a lot 'cause you're-

    14. DDDom D'Agostino51:13

        Yeah.

    15. PAPeter Attia51:13

        I mean, I got a ton. I mean, I would... I had two salads a day when I was on a ketogenic diet because-

    16. DDDom D'Agostino51:17

        Yeah. I'm talking pure carnivore.

    17. PAPeter Attia51:19

        Yeah, I see. I see. Yeah.

    18. DDDom D'Agostino51:19

        Like, they... I mean, f- it's like we're talking-

    19. PAPeter Attia51:22

        Yep, yep

    20. DDDom D'Agostino51:22

        ... steak and water.

    21. PAPeter Attia51:23

        Yep.

    22. DDDom D'Agostino51:23

        Right? Like, not even coffee, not even putting pepper on the steak. Like, there are a group of people who believe that, and it's working for them, and they have, they have a lot of anecdotal data, you know, to support that. And I get, I get an inbox full of people that say, "Hey, look, I had this condition or that condition. I followed carnivore, and here's my blood work." And I can't argue with that.

    23. PAPeter Attia51:43

        Yeah, no, I, I-

    24. DDDom D'Agostino51:44

        Yeah

    25. PAPeter Attia51:44

        ... I, I would, I find that stuff pretty compelling from an-

    26. DDDom D'Agostino51:47

        Mm-hmm

    27. PAPeter Attia51:47

        ... elimination diet perspective. And, and I've, I've certainly met a number of folks who, who feel that way. And, um, yeah, I mean, I, I think, again, it's quite binary. It either it works or it doesn't.

    28. DDDom D'Agostino51:57

        Yeah.

    29. PAPeter Attia51:57

        And for many of these people, they're so debilitated-

    30. DDDom D'Agostino51:59

        Mm-hmm
11. 53:10 – 1:06:31

    Early exogenous ketones

    1. PAPeter Attia53:10

       All right, let's go back to now talk about this world of exogenous ketones-

    2. DDDom D'Agostino53:15

       Mm-hmm

    3. PAPeter Attia53:15

       ... these supplemental ketones. Now, you alluded to them already through the lens of kickstarting a ketogenic diet. But before we talk about application, I want to kind of orient people to the journey you've been on. Um, I was once on-

    4. DDDom D'Agostino53:29

       Mm-hmm

    5. PAPeter Attia53:29

       ... that journey with you being a-

    6. DDDom D'Agostino53:31

       Yeah

    7. PAPeter Attia53:31

       ... uh, a, a regular consumer of all sorts of these things. Um, I will say lately, and I-- when I mean lately, I mean only in the past three months, I recently, uh, tried a product, uh, that I like. I put it in my coffee in the morning, and I believe it is a diester of 1,3-butanediol.

    8. DDDom D'Agostino53:52

       Mm-hmm.

    9. PAPeter Attia53:52

       So it doesn't come with sort of the liver toxicity that I think we should talk about-

    10. DDDom D'Agostino53:56

        Mm-hmm

    11. PAPeter Attia53:56

        ... with respect to 1,3-butanediol, which unfortunately seems-

    12. DDDom D'Agostino53:59

        Mm-hmm

    13. PAPeter Attia53:59

        ... to be running rampant right now. Um, but it's a white powder.

    14. DDDom D'Agostino54:03

        Mm-hmm.

    15. PAPeter Attia54:04

        And what's blows my mind about it is when you mix it in water and drink it, it's palatable. It's not delicious. Like, you wouldn't go out of your way to drink it, but it is not horrible the way that most of these synthetic ketones used to taste. So you can just make a shot glass of it, and it's totally reasonable. Alternatively, it's the creamer in my coffee, and it's fantastic. Um, but let's go way back to the beginning.

    16. DDDom D'Agostino54:30

        Yeah, yeah. [laughs]

    17. PAPeter Attia54:31

        So circa 2011-

    18. DDDom D'Agostino54:34

        Mm-hmm

    19. PAPeter Attia54:34

        ... you had basically only two products you could consume, right? You had a beta-hydroxybutyrate monoester. Actually, there were more than that. There was a ketone salt, which we should talk about, and you had an acetoacetate diester. Is that correct?

    20. DDDom D'Agostino54:53

        Yep. BHB monoester and ac- and 1,3-butanediol acetoacetate diester. Two acetoacetates on 1,3-butanediol.

    21. PAPeter Attia55:00

        Okay.

    22. DDDom D'Agostino55:01

        So they're the two esters.

    23. PAPeter Attia55:02

        So just-

    24. DDDom D'Agostino55:02

        Yeah

    25. PAPeter Attia55:02

        ... explain to people. I mean, I... unfortunately, we have to get into a little biochemistry here for you to explain the difference between esters and salts. And so to everybody listening, apologies. But if you want to, if you want to understand these things, and you have to if you want to be a consumer of them, because everybody is talking about these things as though they're the same, and they're categorically not the same. Um, and most people have no idea what they're talking about, and most people who are selling these things are not being transparent about what it is you're buying. They just call everything a ketone.

    26. DDDom D'Agostino55:34

        Yeah. [laughs]

    27. PAPeter Attia55:35

        So Let's do a little bit of biochemistry, Dom.

    28. DDDom D'Agostino55:38

        Sure. Yeah, glad to do that. Uh, I think it's maybe even good to step back a little bit, uh, because if you go to clinicaltrials.gov and you search ketone supplement MCT, so that, that's a, that's a eight to 10 carbon fatty acid that can convert to ketones. So that's, that might, that'll come into the conversation, but I want to throw it. But one of the original kind of ketogenic substances was one, three butanediol. And I have, uh, I think compliments of Ken Ford, some of the MIT reports of, you know, testing this compound that were in the 1960s. And then there was a report written, uh, by people at NASA where they were basically looking at this as a long duration space flight food. One, three butanediol, which is an alcohol. It's a dialcohol or a glycol. So, uh, it is remarkably ketogenic, which means you consume it and you elevate beta-hydroxybutyrate, and, uh, it's incredibly stable, so hence, you know, for long duration space flight. It was reject- oh, also, it, it preserves food. [chuckles] So in the report, they basically soaked-- they put it into some biscuits, and the biscuits were, like, extremely shelf stable. So it's a humectant, which means it keeps, uh, food moist. And it, uh, it's actually grass-approved to be, uh, like, they put it in sausage casings and things like that, right? So that existed. That was one, three butanediol. And I think, you know, I would say doctor-- There was two people who really I'd like to credit, Dr. Henri Bruninggrabber from Case Western and Dr. Richard Veech, the late Dr. Richard Veech, who was-

    29. PAPeter Attia57:16

        Oh, he passed away

    30. DDDom D'Agostino57:16

        ... a mentor of mine. Yeah, he passed away, like, two or three years ago-
12. 1:06:31 – 1:11:46

    The progression of exogenous ketones: why BHB monoesters & ketone salts emerged as better alternatives

    1. PAPeter Attia1:06:31

       So the monoester is beta-hydroxybutyrate with a monoester bond to one, three-butanediol?

    2. DDDom D'Agostino1:06:39

       Uh, yeah, or vi- yeah, one, three-butanediol that's, yeah, bounded to beta-hydroxybutyrate. But you said it in-- Yeah.

    3. PAPeter Attia1:06:44

       Yeah.

    4. DDDom D'Agostino1:06:44

       So you could say it either way. Yep.

    5. PAPeter Attia1:06:46

       And why is it that you don't experience the same negative issue with that molecule? Is it because you just consume less of it because you're getting the one, uh, you're, you're getting the BHB directly?

    6. DDDom D'Agostino1:06:57

       Yeah. You could take, you know, half the amount and, and get... And then the kinetics are a little bit slower too, 'cause you have to hydrolyze the BHB from that in the liver.

    7. PAPeter Attia1:07:07

       And why can't you just consume BHB? Why is-- Is that not stable enough by its own-

    8. DDDom D'Agostino1:07:11

       No, you, oh-

    9. PAPeter Attia1:07:11

       ... other than in a salt?

    10. DDDom D'Agostino1:07:12

        Uh, you can. Yeah. So there's a free acid and that-- I tinkered with that originally. With the free acid, 'cause you could buy it. And it's super acidic and it's not very stable in solution.

    11. PAPeter Attia1:07:22

        Got it.

    12. DDDom D'Agostino1:07:23

        And for a variety of different reasons, although you could put free acid, it needs to be liquid into, like, an electrolyte formulation. So we gravitated towards, uh, at the time, I was using in my electrophysiol- electrophysiology experiments, you can't put a ketone ester in the bath, right? Because, uh, it doesn't... it needs to be metabolized by the liver. So you can't put it onto neurons, so you have to use the salt. So you mimic, you know, the pharmacokinetics of what you get with the ester.

    13. PAPeter Attia1:07:49

        Mm.

    14. DDDom D'Agostino1:07:50

        So we were putting sodium beta-hydroxybutyrate in, and I was thinking, "Okay, I'll give this to the animals," but then it was like, okay, I'll... I have to-- I was very concerned with the sodium overload. Like, you know, uh, you know, uh, hypertension, all the negative-

    15. PAPeter Attia1:08:05

        Yep

    16. DDDom D'Agostino1:08:05

        ... effects about salt. But all the negative effects about salt, and your listeners may not know this, but most physiologists kind of do that study at the salt-sensitive people or the, the problem with salts, and people maybe even think ketone salts, is that when you consume salt, you get hypertension, and some people are salt sensitive. But that's specific to sodium chloride. So sodium bicarb, sodium citrate, n- uh, sodium beta-hydroxybutyrate is what I'm talking about. If you consume large doses, gram molecules of that, you're not-- that doesn't have the same-

    17. PAPeter Attia1:08:36

        Why is that?

    18. DDDom D'Agostino1:08:36

        ... uh, hypertensive. Something about chloride, so sodium chloride. So you could use potassium chloride, you know, instead of sodium chloride for salt. But I, but I think that's an important thing to consider, uh, because a lot of people shy away from ketone salts because it's sodium, but the salt sensitive sort of hypertension that you get is, is pretty much is, is associated with sodium chloride. Uh, so I-- and I was communicating with Patrick Arnold at the time, [chuckles] and we were-- I kind of have... I was like, "If I have sodium chloride," but I wanted to get potassium chloride, but I looked, I couldn't buy it from Sigma. It wasn't in the CAS database, and nobody had thought about this. I could-- like, how could nobody have thought about putting ketones on different electrolytes? It just wasn't out there. So, um, so I kind of had the idea of, like, sodium, calcium, potassium, uh, magnesium, you know, so there's different things that you can combine.

    19. PAPeter Attia1:09:32

        So you just needed a positive cation.

    20. DDDom D'Agostino1:09:36

        Yeah. And I wanted to balance the potassium, uh, the sodium with potassium. So that was my original thing. I was like, I was going to create a ketone salt and just balance the sodium with potassium-

    21. PAPeter Attia1:09:47

        And are those covalently bound or not? You don't covalent-

    22. DDDom D'Agostino1:09:50

        Ionically bound. Yeah.

    23. PAPeter Attia1:09:50

        Ionically bound.

    24. DDDom D'Agostino1:09:51

        Right. Yeah.

    25. PAPeter Attia1:09:51

        Okay. So again, just-

    26. DDDom D'Agostino1:09:52

        Sodium's positive.

    27. PAPeter Attia1:09:53

        Try- yeah, trying to get everybody back-

    28. DDDom D'Agostino1:09:54

        It's a cation

    29. PAPeter Attia1:09:54

        ... to high school chemistry.

    30. DDDom D'Agostino1:09:56

        Yeah. [laughs] Yep.
13. 1:11:46 – 1:18:06

    Ketone salts: easing the transition into ketosis, dosing, & how they compare to esters

    1. PAPeter Attia1:11:46

       for people

    2. DDDom D'Agostino1:11:46

       ... ketone supplement.

    3. PAPeter Attia1:11:46

       We should, we should go back to that, Dom-

    4. DDDom D'Agostino1:11:47

       Yep

    5. PAPeter Attia1:11:47

       ... 'cause I think a lot of people have lived that experience, and they don't understand why, right?

    6. DDDom D'Agostino1:11:53

       Yeah.

    7. PAPeter Attia1:11:53

       Which is in the early stages of a ketogenic diet, especially, there's, there's little room for error, where as glucose levels are going down and ketone levels haven't come up enough to fill the gap, you really feel lousy.

    8. DDDom D'Agostino1:12:07

       Yeah. Yeah.

    9. PAPeter Attia1:12:07

       Um, and a- and again, in, in retrospect, uh, you, you can work around that, but it's easy to miss it, and [clears throat] meaning it's easy to miss the mark and therefore suffer that, that, that painful transition, which can last weeks in some people. Um, and therefore using these exogenous ketones can be a very elegant bridge through it so that you don't experience-

    10. DDDom D'Agostino1:12:29

        Mm-hmm

    11. PAPeter Attia1:12:31

        ... the, the, the, the negative side effects of the transition.

    12. DDDom D'Agostino1:12:33

        Yeah. So you have the energetic effects. Uh, if you do a FDG PET scan, you're gonna see, like, less brain glucose, you know, utilization for one thing. And then you have, uh, with the ket- you have the contraction of plasma volume because as you lose water and electrolytes, so that you might have orthostatic hypotension. You just don't-- You get the brain fog. And then you have electrolytes, which are literally, like, molecules that are involved in action potentials and keeping membrane potentials in cells. So, uh, and all these can be kind of mitigated through, um, you know, um- Ketone salts, uh, have, have an advantage over the ketone esters. They also have the advantage because the mineral delays gastric absorption. So when you take a dose of a ketone salt, it does not cause an insulin effect. If you drink a ketone ester or a large dose of 1,3-butanediol, and I've done this before, and you do an insulin measurement, you know, an hour after, that's -- you're going to see your insulin levels increase.

    13. PAPeter Attia1:13:34

        How much would you see it increase in you?

    14. DDDom D'Agostino1:13:36

        So the increase seems to be proportional to the differential. So if you rapidly increase ketones two millimolar, and if you stay under two millimolar, then you don't get the spike in, in insulin. But if you consume it and you get above 1.5 to two millimolar, at least in me and a few other people that did this, then you see this counterregulatory dump in insulin. So... And that would also explain when people drink a large dose of a ketone ester, their glucose levels go down. And it's a bit of a scary situation because I know people have gotten themselves into the situations that when you drink the ketone ester, uh, about two hours later or thereabouts, you can be hypoglycemic and also hypoketotic, which means your ketones come up, you utilize them as fuel, but you've released insulin-

    15. PAPeter Attia1:14:27

        To bring the glucose down

    16. DDDom D'Agostino1:14:28

        ... and that caused peripheral glucose disposal, and then you get into a point where you're running, for example, and then you tank because you don't have-

    17. PAPeter Attia1:14:35

        Any fuel

    18. DDDom D'Agostino1:14:35

        ... and, and you can -- it could trigger a headache. It could -- I mean, as it does with me, uh, if you take a large dose. So there's ways around that.

    19. PAPeter Attia1:14:42

        But you're saying the salt produces that effect much less.

    20. DDDom D'Agostino1:14:46

        The salt does not produce that effect at all, so for a number of different reasons. I think, uh, it's not the rate of rise of ketones in the bloodstream seem to be the predictor of if you're going to release insulin, for one thing. And then there's something about the electrolytes too that maybe delays gastric absorption. And with the salts, you're just not getting that elevation of ketones that's as high and as rapid as you would get with a ketone ester. So these are all things to con- consider.

    21. PAPeter Attia1:15:15

        So in the packet of the, the one that -- what's the brand that you brought for me?

    22. DDDom D'Agostino1:15:19

        Uh, Audacious Nutrition Keto Start.

    23. PAPeter Attia1:15:21

        Okay. So in that packet, you're getting about how many grams of electrolytes? About one gram total?

    24. DDDom D'Agostino1:15:29

        Yeah, total about one gram, like sodium, then calcium, magnesium, potassium, right? And you're getting, uh... So there's different formulations. Your original forma- so the packets are a little bit smaller, about the size of LMNT now, but you're getting about six to 10 grams of pure beta-hydroxybutyrate minus the electrolytes. So a lot of people that say you're getting this amount of ketones, that also includes the electrolytes. So you're getting, you know, depending upon which packet you take, six grams or 10 grams of pure beta-hydroxybutyrate in the two different enantiomers. So that's another thing that we could talk about too. Uh, so ketones come in-

    25. PAPeter Attia1:16:08

        Equal mix of R and D?

    26. DDDom D'Agostino1:16:10

        Uh, yes, a 50/50 ratio of D and the L.

    27. PAPeter Attia1:16:15

        Oh, it's D and L.

    28. DDDom D'Agostino1:16:15

        Or R and, and R and S, right? So, um, you know, I guess you could say there's four different ketone molecules. There's D beta-hydroxybutyrate, the L or the R and S if you use that nomenclature, and then you have the acetoacetate. And beta-hydroxybutyrate does need to break down to acetoacetate to be used in the mitochondria. And then you have acetone, which has some interesting signaling and metabolic effects, surprisingly. So it also correlates really well with seizure control. So we're not -- I'm not forgetting about acetone. It's still -- it's like-

    29. PAPeter Attia1:16:46

        So in somebody my size-

    30. DDDom D'Agostino1:16:48

        Mm-hmm
14. 1:18:06 – 1:25:54

    The differences between D- & L-β-hydroxybutyrate, & how racemic mixtures may elevate ketones longer

    1. DDDom D'Agostino1:18:06

       Potentially, yeah, because you have the D and the L.

    2. PAPeter Attia1:18:07

       What were we doing with our Abbott finger sticks?

    3. DDDom D'Agostino1:18:09

       Measuring D beta-hydroxybutyrate, specifically D.

    4. PAPeter Attia1:18:11

       So does that mean every time we were measuring this, we were probably only capturing half what Cahill was capturing? Or was -- has everybody always measured half?

    5. DDDom D'Agostino1:18:20

       No. Well, okay, so racemic ketones were some of the first ones to come out on the market, and then everybody gravitated to the D enantiomer.

    6. PAPeter Attia1:18:28

       I think we should stop-

    7. DDDom D'Agostino1:18:29

       Right? Yeah

    8. PAPeter Attia1:18:29

       ... Dom, and explain to people what the hell we're talking about.

    9. DDDom D'Agostino1:18:31

       [laughs] Yeah.

    10. PAPeter Attia1:18:31

        I don't think people know what enantiomers are.

    11. DDDom D'Agostino1:18:33

        Yeah. Okay. Uh, so beta-hydroxybutyrate is produced in the body primarily, uh, in the form of D beta-hydroxybutyrate, which is a form, uh, the mirror image of beta-hydroxy-- of D beta-hydroxybutyrate is L beta-hydroxybutyrate. So we say if a, if a beta-hydroxybutyrate supplement is racemic, it has D and it has L in it. So I think of the rac-

    12. PAPeter Attia1:19:01

        But let's go back to what you said a second ago, because I want to make sure-

    13. DDDom D'Agostino1:19:03

        Yeah

    14. PAPeter Attia1:19:03

        ... people understand.

    15. DDDom D'Agostino1:19:03

        It's a mirror image like your hand.

    16. PAPeter Attia1:19:04

        The mirror. It's literally a mirror image. So-

    17. DDDom D'Agostino1:19:07

        A mirror image. Yep

    18. PAPeter Attia1:19:07

        ... so for example, allulose is an enantiomer of fructose.

    19. DDDom D'Agostino1:19:11

        Yeah.

    20. PAPeter Attia1:19:11

        Right? So if you hold -- if you draw fructose-

    21. DDDom D'Agostino1:19:14

        Yeah

    22. PAPeter Attia1:19:14

        ... and you hold it in the mirror What you see is not fructose, it's the reflection of fructose, but that's allulose.

    23. DDDom D'Agostino1:19:20

        Allulose is not an enantiomer.

    24. PAPeter Attia1:19:22

        Oh, it's not?

    25. DDDom D'Agostino1:19:23

        It, it's an epimer.

    26. PAPeter Attia1:19:24

        Oh.

    27. DDDom D'Agostino1:19:24

        It's an epimer.

    28. PAPeter Attia1:19:25

        I always thought that was an enantiomer.

    29. DDDom D'Agostino1:19:26

        No, it's an epimer, so it has a, yeah.

    30. PAPeter Attia1:19:28

        It has a, it has another flip.
15. 1:25:54 – 1:30:34

    How ketosis may boost NAD

    1. DDDom D'Agostino1:25:54

       had no effect on seizures. So my colleague, Dr. Jung Ro, said, "You need to look at acetoacetate. And when you elevate beta-hydroxybutyrate and acetoacetate in a one-to-one ratio, that creates a redox balance." And I do think that's important. Also, people have brought to my attention that when you rapidly spike D beta-hydroxybutyrate, you're causing something called reductive stress. So you have the, the, o- the production of NADH from NAD, and that's actually depleting NAD. A ketogenic diet will boost your NAD. Like, you could take-

    2. PAPeter Attia1:26:26

       Hmm

    3. DDDom D'Agostino1:26:26

       ... uh, NAD supplements. That's something that we're working on, too, because I think a central mechanism in ketogenic diets and supplements is the elevation of NAD. So we're working with NAD compounds, MIB626 and other com- I can't talk about that, 'cause it's through an industry, but there are multiple compounds of stabilized NAD that have interesting and remarkable effects. And we're gonna combine them with various ke- new ketone molecules that we're developing. But NAD is sort of like this hub that is a central player in the benefits of ketogenesis.

    4. PAPeter Attia1:27:00

       But what do you make of the fact that there hasn't been any efficacy of NAD supplementation or even NAD precursors?

    5. DDDom D'Agostino1:27:08

       Yeah.

    6. PAPeter Attia1:27:08

       So NR and NMN have really not yielded any meaningful or measurable benefits. The only thing I've ever seen that looked-

    7. DDDom D'Agostino1:27:14

       Mm-hmm

    8. PAPeter Attia1:27:14

       ... somewhat positive was in the trial that looked at patients with, uh, ALS, and you saw a slightly shorter time to-

    9. DDDom D'Agostino1:27:22

       Yep

    10. PAPeter Attia1:27:22

        ... ventilator use with an NR, uh-

    11. DDDom D'Agostino1:27:26

        I'm aware of that part

    12. PAPeter Attia1:27:26

        ... formulation.

    13. DDDom D'Agostino1:27:27

        Yeah.

    14. PAPeter Attia1:27:27

        But, but, but really, we just haven't seen any benefits. And so what-

    15. DDDom D'Agostino1:27:31

        Yeah. Mm-hmm

    16. PAPeter Attia1:27:31

        ... what do you, what do you attribute that to with respect to the NAD story, and what do you think might be missing if indeed there's efficacy there?

    17. DDDom D'Agostino1:27:37

        Well, uh, I mean, just, I can't say what I'm doing now, but we're running experiments, I think even today. Uh, so there's different NAD molecules that are out, that are stabilized forms of them, that are in clinical trials, I think Phase 2 and maybe Phase 3 clinical trials. Uh, and I'm not gonna mention the comp-

    18. PAPeter Attia1:27:56

        Do you think it's a delivery problem?

    19. DDDom D'Agostino1:27:58

        It's a stabilized-- You have to stabilize NAD, and I think that's important to have it stabilized, 'cause when you consume it, the liver takes a lot of it.

    20. PAPeter Attia1:28:06

        Mm-hmm.

    21. DDDom D'Agostino1:28:07

        And if it doesn't-- you're not taking enough of it in a stabilized form, the liver's very greedy. And, uh, actually, I think it'd be good for non-alcoholic fatty liver disease, so that's another-- Uh, I think NAD could be, uh, important for that. Uh, but I think you have to take a dose that gets past the liver, into circulation, and crosses the blood-brain barrier. And there's a number of different stabilized versions of NAD that are in development and testing, and some of them we're working on, that I think have potential for oxygen toxicity. So we're working on those now, giving acutely and also chronically in graded doses.

    22. PAPeter Attia1:28:42

        Will, will there be other applications for it, Dom, such as the holy grail of giro protection or even just performance enhancement, physical performance enhancement?

    23. DDDom D'Agostino1:28:50

        Yes. So I am convinced that some of the animal literature is pretty g- I want to replicate it. So I'm not going to believe something until I replicate it. So [laughs] uh-

    24. PAPeter Attia1:28:58

        Mm-hmm

    25. DDDom D'Agostino1:28:59

        ... so I think, uh, we have plans to do some exercise studies, uh, oxygen toxicity brain studies. So, um, I do think that you need to give quite a bit of it in a stabilized form-

    26. PAPeter Attia1:29:09

        Mm

    27. DDDom D'Agostino1:29:09

        ... and it needs to get to the muscle. And for me-

    28. PAPeter Attia1:29:12

        Mm

    29. DDDom D'Agostino1:29:12

        ... I'm very interested in it crossing the blood-brain barrier and getting to the brain. Uh, I also think that these things will be more efficacious in the context of energetic metabolic stress. So for someone who's already aged, where your NAD level tanks and goes down, uh, in a linear fashion, like with age, uh, NAD goes down, but also in the con- context of, like, traumatic brain injury or shock or... And these are the things that we study. So I'm not studying NAD as a longevity molecule. I'm studying in the context of rare disorders to military, like, operational stress-

    30. PAPeter Attia1:29:53

        Mm
16. 1:30:34 – 1:34:18

    Emerging evidence for using a ketogenic diet to treat anorexia & other psychiatric disorders

    1. DDDom D'Agostino1:30:34

       before coming here. There's 6,000 public, uh, peer-reviewed publications on PubMed, and over the last year, 717 of them, and there's also 558 registered clinical trials on a ketogenic [laughs] diet on clinicaltrials.gov. I mean, you could look at CAR T therapy as something like this. There's like maybe four or five hundred. I mean, so this is something-

    2. PAPeter Attia1:30:55

       And, and-

    3. DDDom D'Agostino1:30:55

       There's been an explosion

    4. PAPeter Attia1:30:56

       ... are those spread mostly between cancer, metabolic disease?

    5. DDDom D'Agostino1:31:01

       Yeah, I actually wrote d- like, uh, I've been on top of this 'cause I've given, like there's 50 clinic- 40 to 50 clinical trials on psychiatric disorders, so that includes bipolar, schizophrenia, major depression, uh, anxiety disorders, anorexia, uh, alcohol use disorders, alcohol withdrawal, uh, traumatic brain injury, autism, uh-

    6. PAPeter Attia1:31:24

       Anorexia is quite interesting. What do you think-

    7. DDDom D'Agostino1:31:26

       Anorexia is-

    8. PAPeter Attia1:31:26

       What do you think is the, uh, the hypothesis there?

    9. DDDom D'Agostino1:31:29

       Well, anorexia is, uh, a psychiatric disorder. It's the psychiatric disorder that kills more people-

    10. PAPeter Attia1:31:35

        Yes, it's the highest mortality

    11. DDDom D'Agostino1:31:35

        ... than any other psych-- Yeah, yeah.

    12. PAPeter Attia1:31:36

        Yep.

    13. DDDom D'Agostino1:31:37

        So, uh, yeah, there was, uh- A, a number of studies, uh, Guido Frank, he's at University of San Francisco, I believe. Uh, he's an expert in eating disorders, as is my colleague, uh, Dr. Deanna Rancourt, who kind of has a peripheral, like, interest in this. But Dr. Guido Frank is running a study on anorexia. I believe from, uh, what I last heard, can't talk about it too much, but I think some of the data is very encouraging. There was case reports that combined, um, a ketogenic diet with, uh, ketamine, and that put, uh, anorexia into remission, and there's been some, quite a bit of buzz about that. And, uh, uh, for anorexia, typically you steer people away from any kind of dietary restriction with anorexia, right?

    14. PAPeter Attia1:32:25

        Exact- Yeah, that would be traditional thinking.

    15. DDDom D'Agostino1:32:27

        Yeah. But you have, uh, the brain, the effects of the ketogenic diet on neuropharmacology, on the hedonic response, on just stabilizing your mood and other factors that could play into anorexia seem to be at play.

    16. PAPeter Attia1:32:43

        Hmm.

    17. DDDom D'Agostino1:32:43

        I was super skeptical because it flies in the face of everything that I know, you know, and I've, uh, we, we have one of the leading experts at University of South Florida, Deanna Rancourt. I remember talking to her about it, and she, you know, kind of was a little bit skeptical, but the data coming out and, uh, looks very promising and compelling. So there's continuing emerging data on psychiatric disorders, largely funded by the Baszucki group. [laughs] I think exclusively funded by Jen and David, uh, Baszucki, their foundation, and I think they're funding million-dollar studies. There's six of them that I know. Um, you have, uh, Ohio State University, um, uh, Stanford, Oxford, um, Stony Brook, UCSD, UCLA. I think Edinburgh there's a study too. Uh, there's a q- I'm just looking at, like, the different applications. So they are funding many different studies, mostly across severe psychiatric disorders.

    18. PAPeter Attia1:33:38

        And are they doing this with ketogenic diets, ketogenic diets plus supplements, just supplements?

    19. DDDom D'Agostino1:33:44

        Yeah. Uh, primarily the ketogenic diet, although having served as a reviewer, 'cause they have study section, there's, in the pipeline of emerging studies that they're funding, I would say quite a few studies will be incorporating exogenous ketone supplementation. So they see that as an innovative approach, uh, and a necessary approach for the feasibility of therapeutic ketosis, because with a psychiatric disorder, it's really difficult to get someone to adhere to a ketogenic diet with bipolar, with schizophrenia. The, I mean, it's like a nightmare.

17. 1:34:18 – 1:40:25

    Potential cognitive & performance benefits of ketone supplementation, & why pushing ketones too high can be dangerous

    1. PAPeter Attia1:34:18

       Yeah. So if, if an individual-

    2. DDDom D'Agostino1:34:19

       Yeah

    3. PAPeter Attia1:34:19

       ... says, "Look, I'm..." I, I totally understand why a ketogenic diet might have efficacy for weight loss. Um, there could be multiple mechanisms that explain it. But, um, I, there are undoubtedly thousands of people listening to us who have no interest in weight loss. They're, they're, they're at an appropriate weight. They're happy with their weight. But some of the things you've talked about might have piqued their curiosity with respect to performance. Be, let's just start with cognitive performance. Um, can you get all the same benefits of a person who slaves their way through what, you know, I used to do and you, you do and, and maybe, you know, uh, to varying degrees do, uh, where you're, you're on this very, very strict diet? Can they get virtually all of those benefits through judicious use of ketone supplements?

    4. DDDom D'Agostino1:35:07

       Well, uh, it depends. You know, and people don't like that answer, and it's also very context dependent. But I'll say this, that there are benefits that you get from carbohydrate restriction that cannot be replicated with exogenous ketone supplementation. With that said, exogenous ketone supplementation tends to lower blood glucose independent of carbohydrate restriction.

    5. PAPeter Attia1:35:27

       Indep- what about, is it part of the mechanism that you just described earlier where, look, you ingest enough ketones, you're gonna drive insulin enough, that's gonna drive down glucose? Which, by the way, would not be the most desirable-

    6. DDDom D'Agostino1:35:36

       Yeah

    7. PAPeter Attia1:35:36

       ... way to lower glucose.

    8. DDDom D'Agostino1:35:37

       Yeah. Well, that's what I originally thought, right? And, uh, actually I do remember talking with Dr. Veech about this, and his opinion was that you're enhancing insulin sensitivity and, and facilitating glucose disposal by virtue of enhancing insulin sensitivity. But I think it's a combination-

    9. PAPeter Attia1:35:54

       Sure

    10. DDDom D'Agostino1:35:54

        ... of different factors. I think consuming exogenous ketones, uh, influences the liver in ways that we don't understand. So one of, uh, I w- our, the next big project that I want to do is liver metabolomics, uh, giving exogenous ketones, 'cause the liver is the master regulator of metabolism, especially in the context of everything, really. [laughs] Everything that we study. So what I think is happening is that it's decreasing gluconeogenesis. It's decrea- decreasing glycogenolysis-

    11. PAPeter Attia1:36:22

        Okay

    12. DDDom D'Agostino1:36:22

        ... and also simultaneously, uh, enhancing insulin sensitivity for greater glucose disposal. However, if ketones get too high, then you have competition. The, the tissues are basically, uh, happy with, with ketones, and they probably decrease glucose, uh, consumption to some extent. Uh, so, uh, an important message that I want to send is that higher ketones are not advantageous and I think potentially very problematic. So-

    13. PAPeter Attia1:36:52

        Define high in that setting

    14. DDDom D'Agostino1:36:54

        ... we've killed quite a bit of animals [laughs] inadvertently, you know, in early studies by putting them into ketoacidosis with different ketone esters. We've never done that with ketone salts, although we can achieve therapeutic ketosis with ketone salts or MCT. So high ketosis would be in animals, once we get above six or seven, then they start sort of like hyperventilating. They get sluggish, and sometimes we can't bring them back.

    15. PAPeter Attia1:37:19

        Wow.

    16. DDDom D'Agostino1:37:20

        So that has made me a bit scared about, you know, some of the ketone esters, and I think some of them are, could be in the bucket of a drug. And I, I think, especially if used in pediatric population, I think that's important. So higher ketones, it's like, like we don't, we're not shooting to get our glucose to, like, you know, seven, eight millimolars, so we should not... When you, when glucose, there's very powerful homeostatic mechanisms that maintain glucose under normal conditions, right? If we're jacking up our ketonesKetones above two, once you get above two to get to three, four, and five, then you're approaching, uh, energy toxicity. So you have a level of ketones in your blood that's producing energy toxicity. Energy toxicity is defined by an elevation of a metabolite circulating in your blood that is causing a number of things. One is a counterregulatory reaction, which means it's, it's increasing the release of insulin, the secretion of insulin. And your kidneys have to dispose about, dispose of that. And our blood gases and blood pH. Blood pH will start to go down. Your blood will become more acidic. That's not a good thing.

    17. PAPeter Attia1:38:32

        And that occurs once you get above two or three millimole?

    18. DDDom D'Agostino1:38:35

        Above two. Pretty much always kind of above two, maybe three. In the context of supplemental ketosis, so if you're on a ketogenic diet and your glucose is so low, your levels of ketones may approach three or four because of the glucose deficiency that you have in your body. So fat oxidation is so high, it's a very elegant and finely tuned, you know, response that you have, uh, with that. So in that context, you're not-

    19. PAPeter Attia1:39:04

        And presumably it's-

    20. DDDom D'Agostino1:39:05

        ... in an energetic stress

    21. PAPeter Attia1:39:05

        ... sorry to interrupt. It's happening-

    22. DDDom D'Agostino1:39:06

        Yeah

    23. PAPeter Attia1:39:06

        ... slowly enough-

    24. DDDom D'Agostino1:39:07

        Yeah

    25. PAPeter Attia1:39:07

        ... that the, the, the redox reaction to balance your pH is happening.

    26. DDDom D'Agostino1:39:14

        Yes.

    27. PAPeter Attia1:39:14

        So you're gonna-

    28. DDDom D'Agostino1:39:14

        Absolutely. Yep

    29. PAPeter Attia1:39:15

        ... you're gonna blow off enough CO2, I assume, in that situation.

    30. DDDom D'Agostino1:39:18

        Yeah.
18. 1:40:25 – 1:46:37

    Applications for ketone esters, & why ketone salts or MCT-blended formulations may be safer & more practical

    1. DDDom D'Agostino1:40:25

       problematic and in reversing that, but, but it is a problem.

    2. PAPeter Attia1:40:27

       So do you think there's any meaningful application for a BHB monoester these days given the-

    3. DDDom D'Agostino1:40:32

       Oh, yeah. Yep

    4. PAPeter Attia1:40:32

       What is the application for that in your mind?

    5. DDDom D'Agostino1:40:34

       Well, I think it's, it's context dependent, but I think these things can be given, you know, orally or IV in the context of acute situations. So I'm in favor of, uh, ketone esters or more potent ketone molecules for medical applications, quickly elevating ketones under, for example, status epilepticus, uh, traumatic brain injury, like a blast injury.

    6. PAPeter Attia1:40:55

       But I thought you said they didn't work well in epilepsy.

    7. DDDom D'Agostino1:40:59

       It depends. No, I'm talking about maybe a ketone diester of acetoacetate, which we use.

    8. PAPeter Attia1:41:03

       Ah.

    9. DDDom D'Agostino1:41:03

       So, okay, so the monoester. Yeah.

    10. PAPeter Attia1:41:05

        Yeah. I'm talking about the original-

    11. DDDom D'Agostino1:41:06

        Yeah. Mm-hmm

    12. PAPeter Attia1:41:07

        ... the original molecule from, from NIH that was a monoester of BHB.

    13. DDDom D'Agostino1:41:13

        I think they can be formulated. So this comes to a, this comes to, uh, something that's a gap in the literature, and there's a gap because every company or university with IP wants to study a single molecule in isolation. I think what we need to do is actually formulate things, and that's kind of what we do. [laughs] Uh, so every molecule will have pros and cons and caveats, and you could largely mitigate, uh, the problem with ketone esters by, you know, simply mixing it with MCT. Uh, but you're still gonna have the, the 1,3-butanediol issue. You know, if you're consuming that over long periods of time, that is something to consider. But you can also have a glycerol, uh, triester of beta-hydroxybutyrate or acetoacetate. We published, uh, the, the title is, like, Novel Ketogenic Formula where we had a beta-hydroxybutyrate, uh, or, uh, glycerol triester. So we're working with those compounds too, but I, but I think, uh, yeah, it's very context dependent. And the go-to would probably be the electrolyte salts just because you don't want to... For the average person, if you stay into that sweet spot of one to two millimolar-

    14. PAPeter Attia1:42:24

        Yeah

    15. DDDom D'Agostino1:42:24

        ... if you elevate beta-hydroxybutyrate in the blood one millimolar, that represents a 10% increase of available energy to the brain. So we know that roughly speaking.

    16. PAPeter Attia1:42:34

        Yeah.

    17. DDDom D'Agostino1:42:34

        So, uh, so it's all these calculations from the AV difference have been done, so I think that's important. Lactate is also something, uh, to consider.

    18. PAPeter Attia1:42:43

        So when you think about the advantages of lactate for, uh, alternative brain fuel and ketone as alternative brain fuel, you know, I had George Brooks on the podcast a while ago and he talked about how you could probably rescue concussion patients if you administered lactate quickly following a concussion. Would you say the same is likely true for ketones?

    19. DDDom D'Agostino1:43:02

        Yeah. I think lactate's, uh, an incredible molecule. My early studies in 2004 and '05, I think, with lactate. But the ketones represented a more viable option and also had the anti-seizure effects that we had. Plus, I was inspired by the work of, of, of George Cahill and Dr. Veech and, you know, Theodore Van Itallie, and then I got steered towards beta-hydroxybutyrate. But I think an important message is that, uh, formulation is the key. So you have beta-hydroxybutyrate, you have lactate, you have MCTs cross the blood-brain barrier, so it's a type of fat that actually can cross the blood-brain barrier.

    20. PAPeter Attia1:43:40

        Do you still use MCTs for anything?

    21. DDDom D'Agostino1:43:42

        I think MCTs are great. Yeah, I think... You know, I put it, I use a coffee creamer called Keto Brainz. It's like alpha-GPC, MCT You know, theanine has a couple -- it's a mixture of combinations of things. But when you combine a ketone salt with MCT, then you have a mol- you have a formulation that stimulates your own ketone production while you're delivering an exogenous ketone. And if it's a racemic, uh, DL beta-hydroxybutyrate like KetoStart, uh, then you have a sustained ketone delivery system for, you know, you know, half of the day. So you just dose that a couple times. Uh, but also some of the problems that we talked about with fast entry of ketones into the bloodstream with the ketone esters or one, three b- can, if you formulate that with MCT, which we've published on that, that can mitigate, uh, some of the negative effects. So we don't see-- You can mitigate the toxicity, at least in animal models, from, uh... Uh, you need to appreciate the, the rate of rise, uh, of ketones is that's kind of the trigger for some of the counter-regulatory effects, so a slow... So it's kind of more like a dosing issue.

    22. PAPeter Attia1:44:51

        And if you're taking the currently formulated ketone salt that you brought, um, you do not have to worry about the electrolyte load? So if you're consuming three of those a day, that would be three grams of additional electrolytes, which again, based on what you're also getting in your food, a lot of people would say, "Gosh, that's too many electrolytes."

    23. DDDom D'Agostino1:45:08

        Yeah.

    24. PAPeter Attia1:45:08

        But you're not seeing the effect because of the lack of chloride?

    25. DDDom D'Agostino1:45:12

        Yeah. I would say for people that have, like, normal physiology, no kidney, or maybe even with impaired kidney function because, you know, there's, uh, KetoCitra is, is sold. I think a study just came out with beta-hydroxybutyrate citrate for, uh, and other electrolytes too for, for kidney disorders. But generally, no. So I was concerned that sodium would cause hypertension-

    26. PAPeter Attia1:45:35

        Yep

    27. DDDom D'Agostino1:45:35

        ... and an increase, but, uh, sodium chloride seems to be the, the major player there. So I would say no, but also do your blood work. Uh, I haven't seen that, and that was one of the early concerns I had. Actually, it steered me toward developing something other than sodium, uh, to potassium and calcium and other. So electrolytes are largely, you know, uh, benign unless you're above the 10 grams per day kind of issue. And I think even with sodium, uh, the guidelines are something like five grams of sodium per day, like dietary sodium. But then something just came out that said, like, that's sh- should probably be more like eight to 10, you know? Could start to be considered.

    28. PAPeter Attia1:46:18

        Where, where-

    29. DDDom D'Agostino1:46:18

        But five's kind of high

    30. PAPeter Attia1:46:18

        ... which guideline?
19. 1:46:37 – 1:59:31

    The role of a ketogenic diet in treating cancer

    1. PAPeter Attia1:46:37

       two particular applications with ketogenic diets, both of which-- well, one of which you've spoken about a little bit. The other one we've sort of talked about, um, kind of indirectly. But let's, let's say a word about what you think the future is for ketogenic diets and the treatment of cancer, and then separately for the treatment of dementia, specifically-

    2. DDDom D'Agostino1:46:54

       Yeah

    3. PAPeter Attia1:46:54

       ... potentially Alzheimer's disease, but any form of dementia.

    4. DDDom D'Agostino1:46:57

       Yeah. Uh, we had a review come out with 49 authors, and the title was, uh, Ketone Metabolic Therapy Framework for Glioblastoma. Uh, so there was, you know, that includes basic science researchers, a number of oncologists at major cancer centers and stuff. So the gist of that, uh, the-- I think it's really important to focus on cancers that, where the standard of care doesn't work. So advanced metastatic cancer, obviously pancreatic and glioblastoma. But glioblastoma has always been sort of the heart of what we're studying. Uh, and I think the idea is to make metabolic therapy part of the standard of care. So the general gist with that review, and the senior author is Dr. Thomas Seyfried.

    5. PAPeter Attia1:47:43

       Mm-hmm.

    6. DDDom D'Agostino1:47:43

       I know you've had him on the podcast. And, uh, Tomas Durock or Durai, uh, he was the primary author. Uh, in that, in that review, it creates a framework that has, uh-- There's so much in that review. It ended up-- It was like 200 pages carved down to like 50 pages with about 1,000 references, right? So just like short, making it super concise explanation. So the gist of that for ketone metabolic therapy for cancer management, specifically glioblastoma, but we think similar reviews can be written for other types of cancers that are specifically like hot, that are highly glycolytic and have the Warburg effect, so really high on an FDG PET scan. So above like 2.5 SUVs like on a PET scan would define it as hyperglycolytic. Achieve and maintain a glucose ketone index of one to four. So that's the millimolar concentration of glucose over ketones. So if your glucose was four, which is relatively normal, and your ke-

    7. PAPeter Attia1:48:45

       Eighty. Yeah

    8. DDDom D'Agostino1:48:45

       ... and your ketone levels were one, you know, which is probably-

    9. PAPeter Attia1:48:48

       You're at the entry of that zone

    10. DDDom D'Agostino1:48:49

        ... where I'm at now, so that gives me a GKI of four. Standard American di- uh, diet produces of like a GKI of 50, right? [chuckles] Or 40 or 50.

    11. PAPeter Attia1:48:57

        Yeah, yeah.

    12. DDDom D'Agostino1:48:58

        So, so simply the, the guidelines are one to two, but I think that's too strict. Achieving a glucose ketone index of one to four is the base of, the basis of the therapy, and that sets the stage for other modalities to work. Uh, for example, you could have, uh, you want to then target glucose and glutamine with various drugs. And if we're gonna talk about anti-glycolytic drugs, uh, metformin. We've done quite a bit of research with metformin, and I think that's a great molecule. Could be a synergizer. I also think of that as a redox, and I'll come to that.

    13. PAPeter Attia1:49:35

        But let me ask a point-blank question, Dom.

    14. DDDom D'Agostino1:49:37

        Uh-huh.

    15. PAPeter Attia1:49:37

        Um, glioblastoma carries with it a mortality rate of 100%.

    16. DDDom D'Agostino1:49:41

        Yep.

    17. PAPeter Attia1:49:42

        So it's been said that any patient who survives a glioblastoma has been misdiagnosed. They didn't have glioblastoma. I mean, meaning it's just, it's, it's one of the cancers that really gives cancer a bad name. Is there any evidence that any form of ketogenic diet, even at a one-to-one ratio of glucose to ketone, is going to produce a durable remission in a patient with a GBM?

    18. DDDom D'Agostino1:50:05

        Durable-- no, it's not gonna cure it. So we're talking about the standard of care does nothing. We're talking about, you know-

    19. PAPeter Attia1:50:11

        Life extension.

    20. DDDom D'Agostino1:50:12

        Yeah. We're talking about doubling survival, like tripling, and then as we learn more. So the, the ketone metabolic therapy framework for GBM is like the first document in a series of documents that will ultimately be, you know, version number three will be using-

    21. PAPeter Attia1:50:31

        Are there any RCTs?

    22. DDDom D'Agostino1:50:32

        ... AI platforms to like, you know, d- to decode the genetics for personalized therapy.

    23. PAPeter Attia1:50:36

        But are there, are there RCTs that have-

    24. DDDom D'Agostino1:50:38

        Mm-hmm.

    25. PAPeter Attia1:50:38

        And, and what-

    26. DDDom D'Agostino1:50:38

        Yeah

    27. PAPeter Attia1:50:38

        ... in an RCT when you place full standard of care versus full standard of care plus ketogenic therapy-

    28. DDDom D'Agostino1:50:44

        Mm-hmm

    29. PAPeter Attia1:50:44

        ... what is the difference in median survival?

    30. DDDom D'Agostino1:50:46

        Yeah, those studies are ongoing now. Jethro Hu at UCLA just published a study, uh, at UCLA just showing, you know, improved metrics of survival and, you know, uh, increased quality of life and different... And I didn't get a chance to-- It just came out.
20. 1:59:31 – 2:09:45

    The potential of a ketogenic diet for treating Alzheimer’s disease

    1. PAPeter Attia1:59:31

       Um, let's talk about Alzheimer's disease.

    2. DDDom D'Agostino1:59:33

       Okay.

    3. PAPeter Attia1:59:34

       So equally devastating.

    4. DDDom D'Agostino1:59:36

       Yeah.

    5. PAPeter Attia1:59:36

       Much longer tail. But in my mind, seems somewhat easier to address through metabolic therapies-

    6. DDDom D'Agostino1:59:41

       Mm-hmm

    7. PAPeter Attia1:59:41

       ... because at least in the subset of those patients for whom an energetic crisis is at the core, and I don't think that that's all cases. I think it's a-- I think that's also a very heterogeneous disease. But at least one subset of these people are probably in an energetic crisis. What, what do we know about the current research, and what's the current state of affairs for using ketogenic therapies?

    8. DDDom D'Agostino2:00:04

       Yeah. Well, uh, you're familiar with the Alzheimer's drugs, right? And, you know, uh, there's been not a whole lot of movement there. We have the antibodies. You know, you go to antibody therapy, you're talking 50K at least. You know, hundreds of thousands of dollars. You have the potential for side effects like cerebral hemorrhage and things like that. And they move the needle maybe for prevention. Uh, a hallmark characteristic of Alzheimer's disease is glucose hypometabolism, so that is actually being part of the criteria for evaluating. Uh, my thoughts are that in communicating with hundreds of people with Alzheimer's and c- and communicating with people that do dietary therapies is that there's a subset of people with Alzheimer's disease or let's just call it dementia, right? Because Alzheimer's is still a pretty fuzzy diagnosis, you know, uh, [chuckles] clinically. And we have the f-- we have the PET scans to look at amyloid, and then there's p-tau and, and other things. Um, but I think, I think it's better to put it under the umbrella of, you know, uh, mild cognitive impairment. I think it's important to focus on that and advance Alzheimer's disease. So a ubiquitous characteristic is glucose hypometabolism. So, um, we are under-- I've always been under sort of the, the impression that, uh, the accumulation of amyloid and tau are a consequence, are downstream epiphenomenon [chuckles] of inflammation, neuroinflammation. Uh, there's of course huge ge-- I think there's like 50 different genes or, you know, that can cause Alzheimer's genes. So if we're talking about APOE4 carrier, that's like f- I don't know, 80% likely to get, you know, advanced Alzheimer's or early onset Alzheimer's disease.

    9. PAPeter Attia2:01:50

       If, if you have two, if you have two copies, um-

    10. DDDom D'Agostino2:01:52

        Yeah, if you have like two co- or even one copy, I think it's like 40.

    11. PAPeter Attia2:01:53

        Yeah, maybe even a bit less than that.

    12. DDDom D'Agostino2:01:54

        Yeah.

    13. PAPeter Attia2:01:54

        But one, one copy is, is-

    14. DDDom D'Agostino2:01:56

        If you have two copies, you are destined to have it. I mean-

    15. PAPeter Attia2:01:59

        No.

    16. DDDom D'Agostino2:01:59

        Well, uh-

    17. PAPeter Attia2:02:00

        If you have-- There's really only-- Th-th-there are a handful of genes in which you are destined to get it-

    18. DDDom D'Agostino2:02:04

        Yeah

    19. PAPeter Attia2:02:04

        ... uh, unfortunately at this point. Um, you know, PSEN1, PSEN2, APP.

    20. DDDom D'Agostino2:02:08

        Yeah. Destined is a strong word. Like if you do nothing.

    21. PAPeter Attia2:02:11

        But, but again, I mean, you know, 25% of the population are heterozygous-

    22. DDDom D'Agostino2:02:16

        Yeah

    23. PAPeter Attia2:02:16

        ... for APOE4.

    24. DDDom D'Agostino2:02:17

        Yep.

    25. PAPeter Attia2:02:17

        And, and their, you know, their risk is twofold higher.

    26. DDDom D'Agostino2:02:20

        Mm-hmm.

    27. PAPeter Attia2:02:21

        But, but I, you know, I don't think anyone would consider that Sort of destiny

    28. DDDom D'Agostino2:02:24

        Yeah. Your genes are not your destiny. I don't want to make that sort of assumption, but, uh, it puts you at greater risk for sure. So, um, I think, you know, just taking a step back that we-- I think inflammation is the major driver. The more-- And that wasn't even on my radar probably the last time we talked-

    29. PAPeter Attia2:02:43

        Mm-hmm

    30. DDDom D'Agostino2:02:43

        ... or maybe 10 years ago. But I do think that, uh, systemic inflammation leads to neural inflammation and, uh, you know, we know that if we take mice or if we take humans or take mice and inject LPS, we can rapidly cause, uh, amyloid progression. Like, and so those studies have been done. So, uh, metabolic-based therapies, ketogenic therapies, you know, diet, these things, um, not only change metabolic physiology and brain energy metabolism, but they change-- they reduce systemic inflammation. And I don't know if you measure your, you know, inflammatory markers like HSCRP. Mine is even non-detectable. You know, I, I'll even do things like work out really hard and go, and it's pretty much low. It only was elevated when I lived in an undersea environment and was breathing hypercapnic, you know, and under a lot of stress. But I, but I think, uh, the advantage of ketogenic metabolic therapies for Alzheimer's disease is, uh, really hinging upon suppressing inflammation, improving glucose metabolism, and, and elevating ketones to increase, uh, symptomatically brain energy metabolism. Uh, so I think these are good things-
21. 2:09:45 – 2:11:26

    Tools for cognitive enhancement: ketones, alpha-GPC, MCT, caffeine, strategic fasting

    1. DDDom D'Agostino2:09:45

       a source of energy.

    2. PAPeter Attia2:09:46

       What do you think they're best taken with?

    3. DDDom D'Agostino2:09:48

       Ketones in general?

    4. PAPeter Attia2:09:49

       Oh, no. Sorry.

    5. DDDom D'Agostino2:09:50

       Or-

    6. PAPeter Attia2:09:50

       Alpha-

    7. DDDom D'Agostino2:09:50

       Alpha-GPC?

    8. PAPeter Attia2:09:51

       ... GPC. Yeah.

    9. DDDom D'Agostino2:09:51

       Um, I think it works good with caffeine. So alpha-GPC, MCT, and caffeine, and maybe theanine too, which is, um-- has, like, a, a little bit of a GABAergic effect. Uh, that describes a product called a Keto Brain. So that's, uh, a pretty good product that is kind of a staple product for me. Uh, I ran out of it. I kinda miss it, so I'm gonna-- reminds me I have to go buy that. But, uh, it's been sort of what I sip on. I put that into my coffee and sort of when I'm working on grants or giving lectures or just need long periods of cognitive. But I think alpha-GPC, 'cause maybe a little bit of too much, um, uh, just makes me a little bit too hyper-focused and a little too stimulated, and I think it maybe can affect my sleep, uh, too. So I think people-- I use that as situationally, just as I use fasting now. So I use fasting very situationally, and that's what I recommend to people. It shouldn't be your default. It shouldn't be like, you know, fasting every day 'cause I think the more you do it, uh, the easier it gets. But I think you can actually maybe derive more benefits situationally if you have an inflammation event. Like there's a person, two people that reached out to me that has shingles or, uh, a herpes simplex flare up, and then they fast then. Then it works for that. Or they have a GI, you know, some kind of GI issue-

    10. PAPeter Attia2:11:10

        Hmm

    11. DDDom D'Agostino2:11:11

        ... or some kind of-- Or if they're traveling, or for me, when I'm just, you know, bogged down with a lot of, uh, paperwork, grant reviews, writing grants or something, I'll, I'll fast through-- for half of the day or more of the day, and I'm just sharper. You know, just using situationally.

    12. PAPeter Attia2:11:25

        All right. Let's talk

22. 2:11:26 – 2:20:30

    Hyperbaric oxygen therapy for concussion, TBI, PTSD, & cognitive function

    1. PAPeter Attia2:11:26

       a little bit about hyperbaric oxygen now. You-

    2. DDDom D'Agostino2:11:28

       Yeah

    3. PAPeter Attia2:11:28

       ... mentioned and alluded to the fact that there are a handful of FDA indications for them. To me, the two most-

    4. DDDom D'Agostino2:11:33

       Mm-hmm

    5. PAPeter Attia2:11:33

       ... apparent would be treatment of the bends and obviously for burn, uh, for burn patients.

    6. DDDom D'Agostino2:11:38

       Yep.

    7. PAPeter Attia2:11:38

       So it dramat-dramatically, um, aids with wound healing. But there are many things that are conspicuously absent from any FDA approval, right? There's no FDA approval for TBI. There's no FDA approval for concussion. There's no FDA approval for anything giro protective. And yet, I've always, um, said every time I've done-- gone back, and I maybe do this every two years. I go back and look at the data around concussion and TBI that you-- It depends how you look at the data. There could be a case for it. And, you know, patients are always asking me about hyperbaric oxygen. It's truly one of the things I get asked about the most. And I generally ter-tell patients it's not worth the cost. It's not worth the hassle. It's not worth the inconvenience. The only except-- outside of the approved FDA indications, the only thing I would suggest going against the FDA recommendation is if I were to have a concussion, if one of, one of my kids had a concussion, I would probably say the downside of hyperbaric oxygen is low enough. I think the potential upside is there. I think it's worth the risk. Uh, first of all, do you agree with that statement? If not, modify it.

    8. DDDom D'Agostino2:12:51

       In the context of, uh, acute concussion or a brain injury, I-

    9. PAPeter Attia2:12:55

       Let's start with the concussion and then, yeah-

    10. DDDom D'Agostino2:12:57

        Yeah

    11. PAPeter Attia2:12:57

        ... talk brain injury after.

    12. DDDom D'Agostino2:12:58

        Uh, yeah. In the context of acute, like within the first forty-eight to seventy-two hours, I think hyperbaric oxygen can be remarkably effective in-- for kids and for younger popu-- and probably effective for adults if early. The jury-

    13. PAPeter Attia2:13:15

        What protocol would you recommend in that situation?

    14. DDDom D'Agostino2:13:17

        Yeah. I would-- Well, if it's a penetrating traumatic brain injury as-

    15. PAPeter Attia2:13:22

        No. Blunt.

    16. DDDom D'Agostino2:13:22

        Okay. Okay. Uh-

    17. PAPeter Attia2:13:23

        Yeah, blunt, blunt. We're not military. [laughs]

    18. DDDom D'Agostino2:13:24

        Yeah. Okay. [laughs] Yeah. So, uh, I would go with, like, standard protocol, like two atmospheres of oxygen, you know, sixty to ninety minutes, five days a week, uh, you know, minimum maybe three days a week, forty, forty dives over that period of time, um, I think would be-- could be potentially, uh, bene-

    19. PAPeter Attia2:13:44

        That's a lot

    20. DDDom D'Agostino2:13:44

        ... beneficial. Yeah, that could be-

    21. PAPeter Attia2:13:46

        That's a hell of a lot. That's-- You're talking two months.

    22. DDDom D'Agostino2:13:49

        Yeah. Forty sessions, that's, that's like the most. Like, I mean, maybe you could probably maybe even get by with, like, five sessions.

    23. PAPeter Attia2:13:54

        And, and you can understand why I don't recommend people do this.

    24. DDDom D'Agostino2:13:57

        Yeah.

    25. PAPeter Attia2:13:57

        Like, that's a, that's a job.

    26. DDDom D'Agostino2:13:58

        Yeah. That-

    27. PAPeter Attia2:13:59

        You, you just basically decided you're not working for a month because if you gotta drive thirty minutes each way-

    28. DDDom D'Agostino2:14:04

        Yeah

    29. PAPeter Attia2:14:04

        ... and you're gonna spend ninety minutes in it, that's two and a half hours-

    30. DDDom D'Agostino2:14:08

        Yeah
23. 2:20:30 – 2:25:26

    Peter’s takeaways

    1. PAPeter Attia2:20:30

       great to hear. Dom, this has been, um, really interesting. I mean, to me There have been a lot of things that unfortunately haven't changed fast enough since we last spoke, namely around our insights around cancer and Alzheimer's disease, largely due to a lack of clinical trials. But the unbelievable change in exogenous and supplemental ketones, it's, it's exploded. You've been leading the charge in that. It gives someone like me a lot of hope. I mean, I've long ago given up on the, uh, the discipline of a ketogenic diet, although I, I, I achieved remarkable benefit from it. Um, but, but something just changed when my daughter was old enough and I just wanted to start eating everything, um, and that hasn't vanished. So I'm on the, uh, I'm on the See Food diet. That is S-E-E Food diet. I eat all I see.

    2. DDDom D'Agostino2:21:18

       And, and you're not managing epilepsy or anything like that.

    3. PAPeter Attia2:21:21

       Yeah, yeah.

    4. DDDom D'Agostino2:21:21

       Yeah, you got benefits of it.

    5. PAPeter Attia2:21:22

       Yeah.

    6. DDDom D'Agostino2:21:22

       And I know at the time, like I distinctly remember going to the gym with you and the amount of like volume that you would do or just, you know, just riding the bike and just swimming and j- yeah, [laughs] it's just-

    7. PAPeter Attia2:21:31

       Yeah, yeah

    8. DDDom D'Agostino2:21:31

       ... it was crazy.

    9. PAPeter Attia2:21:32

       But I really, I, I-- you've really piqued my curiosity about these, um, exogenous ketones and, and in addition to that one that I've just started putting into my coffee, I think I'm gonna really give some of these salts a try, um, especially given what you've said about the-- 'cause I ha- you know, I'd always felt that, well, I need to kind of be somewhat mindful of, of, of, of electrolyte load beyond what I already consume.

    10. DDDom D'Agostino2:21:54

        Mm-hmm.

    11. PAPeter Attia2:21:54

        Um, and also, although we didn't talk about it, I know you and I have spoken about it just before, which was you don't have the same GI consequences that used to exist with the ketone salts, which largely limited their consumption. So, uh, tell me, tell me and tell everybody again the, the brand that, that you're-

    12. DDDom D'Agostino2:22:09

        Mm-hmm

    13. PAPeter Attia2:22:09

        ... suggesting I give a try to that you brought.

    14. DDDom D'Agostino2:22:12

        Yeah. Uh, Keto Start by Audacious Nutrition is one.

    15. PAPeter Attia2:22:15

        Keto Start.

    16. DDDom D'Agostino2:22:16

        Yeah, Keto Start.

    17. PAPeter Attia2:22:17

        You can buy it online.

    18. DDDom D'Agostino2:22:18

        Yeah.

    19. PAPeter Attia2:22:18

        It's direct-- Do you buy it directly from them?

    20. DDDom D'Agostino2:22:19

        Yeah, you can get it-

    21. PAPeter Attia2:22:20

        Is it on Amazon?

    22. DDDom D'Agostino2:22:20

        ... right on the-- I think, yeah, it's on Amazon. It should be on Amazon.

    23. PAPeter Attia2:22:22

        Okay, great.

    24. DDDom D'Agostino2:22:23

        So yeah. So I mean, that's what I use and it's kind of evolved out of, uh, you know, it was essentially the molecules that we originally studied and kind of stuck with even after, you know, looking at all the different ketone esters.

    25. PAPeter Attia2:22:35

        And you, you're not financially involved in this company?

    26. DDDom D'Agostino2:22:37

        No. No, I'm not.

    27. PAPeter Attia2:22:38

        Your wife advises them, though?

    28. DDDom D'Agostino2:22:39

        Yes, my-

    29. PAPeter Attia2:22:39

        Yep. Okay.

    30. DDDom D'Agostino2:22:40

        So, uh, so yeah, I've been more-- I, I'm on the sidelines, so I don't sell anything. [laughs] So I don't have any companies. I don't sell anything. I do advise for, for companies, and we talked about CGM, so I'm an advisor for Levels Health. I'm an advisor for MedPsy, M-E-T-P-Y-S. So it's, uh, essentially an app and a program for metabolic psychiatry and advise a little bit for, uh, RX Sugar, which sold allulose, so I sh- kind of disclose those things. So I don't think we talked about allulose too much, but, um, [laughs] yeah, so I don't-

Episode duration: 2:25:27