The Peter Attia Drive
#375 - The ketogenic diet, ketosis, and hyperbaric oxygen: metabolic therapies for weight loss, cognitive enhancement, cancer, Alzheimer's disease, brain injuries, and more | Dominic D'Agostino, Ph.D.
08 Dec 2025
View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Dom D'Agostino is a neuroscientist and professor at the forefront of metabolic therapies, including ketogenic diets, exogenous ketones, and hyperbaric oxygen. In this episode, Dom breaks down nutritional versus supplemental ketosis, defines meaningful ketone thresholds, and outlines practical ways to achieve ketosis. He explains how a ketogenic diet can support metabolic health and weight loss, and advises on how to maintain adequate protein and avoid common mistakes. Dom surveys the growing landscape of exogenous ketones—from salts and esters to 1,3-butanediol—and effective pairings like caffeine, MCT oil, and alpha-GPC. He highlights the role of ketogenic therapy in cancer (particularly glioblastoma) and its promise for neurodegenerative diseases. The conversation also covers recommended hyperbaric oxygen protocols for brain injuries and cognitive function, situations where fasting or ketones offer cognitive and anti-inflammatory benefits, and touches on the carnivore diet as a ketogenic variant with potential relevance for autoimmune and metabolic conditions. We discuss: Dom and Peter's shared interest in ketosis, and Dom's scientific journey [2:30]; Dom's work for the Navy on oxygen toxicity [7:00]; Nutritional ketosis defined: physiology, biomarkers, and how fasting and diet generate therapeutic ketones [15:00]; The historical roots of ketogenic diets in epilepsy treatment, and evidence showing ketones reduce seizure activity and strengthen brain resilience [19:00]; Dom's personal experience on the ketogenic diet: tracking macros, getting enough protein, and monitoring ketone levels [24:15]; Using a ketogenic diet for weight loss: Dom's guidance on protein, fiber, calorie tracking, lipid monitoring, and more [31:00]; Protein on ketogenic diets: Dom's rationale for higher intake and muscle preservation [38:00]; Incorporating carbohydrates into keto: timing, high-fiber foods, and other considerations [41:30]; The carnivore diet: whether this diet induces ketosis, how it functions metabolically, and why it may help individuals with autoimmune conditions [44:15]; Early exogenous ketones: how 1,3-butanediol works, its liver toxicity risk, and why ketone esters replaced it [48:15]; The progression of exogenous ketones: why BHB monoesters and ketone salts emerged as better alternatives to 1,3-butanediol for ketone supplementation [59:30]; Ketone salts: easing the transition into ketosis, dosing, and how they compare to ketone esters [1:04:00]; The differences between D- and L-β-hydroxybutyrate, and how racemic mixtures may elevate ketones longer and offer unique biological effects [1:09:30]; How ketosis may boost NAD, and why NAD supplements have fallen short so far [1:16:30]; Emerging evidence for using a ketogenic diet to treat anorexia and other psychiatric disorders [1:20:30]; Potential cognitive and performance benefits of ketone supplementation, and why pushing ketones too high can be dangerous [1:23:45]; Applications for ketone esters, and why ketone salts or MCT-blended formulations may be safer and more practical for most people [1:29:15]; The role of a ketogenic diet in treating cancer [1:34:45]; The potential of a ketogenic diet for treating Alzheimer's disease [1:45:45]; Tools for cognitive enhancement: ketones, alpha-GPC, MCT, caffeine, strategic fasting, and more [1:53:45]; Hyperbaric oxygen therapy for concussion, TBI, PTSD, and cognitive function, including protocols and dosing approaches [1:55:30]; Peter's takeaways, recommended products, and additional resources to learn more [2:03:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
Chapter 1: What is the focus of this podcast episode?
Hey everyone, welcome to The Drive Podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen.
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If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peteratiamd.com forward slash subscribe. My guest this week is Dom D'Agostino.
Dom is a neuroscientist and professor at the forefront of metabolic therapies, including ketogenic strategies, exogenous ketones, and hyperbaric oxygen. In this episode, we discuss nutritional versus supplemental ketosis, clear definitions, thresholds for clinical ketosis, and practical ways to achieve it while keeping protein adequate.
Why the early transition into a ketogenic diet can be challenging and how electrolytes and ketone salts can smooth that on-ramp. The growing landscape of exogenous ketones, the salts versus the esters, 1,3-butanediol, taste and insulin effects, and simple effective pairings such as caffeine, MCT, and alpha-GPC. Ketogenic diets as metabolic therapy for cancer, especially glioblastoma.
the prospects for ketogenic diets in neurodegenerative diseases, including dementia and Alzheimer's disease specifically, hyperbaric oxygen chambers, Dom's recommended protocols, practical barriers, and the rigor of ongoing trials, when fasting and ketones shine as a situational tool for cognition, workload, travel, and inflammation, and the carnivore diet as a ketogenic variant and what it implies for certain autoimmune and metabolic conditions.
So without further delay, please enjoy my conversation with Dom D'Agostino. Hey Dom, thank you for making the trip out to Austin. It's, boy, it has been a long time since we've been in person. I'm afraid to hazard a guess as to when, but I know you and my brother see each other a lot more and I'm always getting pictures of you visiting him and him visiting you.
Yeah, yeah. Paul's amazing. He's a mentor to me and as you are through the health and Paul's like an amazing entrepreneurial mentor and a life mentor in many different ways. So great to see you both. You guys are such uber high achievers in different domains. And I think 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.
Well, the same can be said for you. Dom, you've been on the podcast a couple of times, but I know that in podcast land, A, we've probably got hundreds of thousands of listeners today that weren't listeners the first and second time you were on the podcast. And frankly, those that were, I think it would be understandable that they've forgotten most of what we've spoken about.
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Chapter 2: How does Dom D'Agostino define nutritional ketosis?
Good question. So hyperbaric oxygen, you experience that with hyperbaric oxygen therapy. And there's 14 different FDA approved applications. In that context, you only go to about a maximum of 2.5 to 3 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.
You're breathing high concentrations of oxygen and at 50 feet of seawater, the potential for oxygen toxicity exists.
Explain to folks exactly what that is. How does a rebreather work? What's the concentration of oxygen that they're breathing in?
Chapter 3: What challenges arise during the transition to a ketogenic diet?
A closed circuit rebreather, for example, like a Draeger rebreather, like the original ones, those early rebreathers, and even now, it's high concentration. It's essentially 100% oxygen. You're breathing 100% oxygen. So there's no nitrogen. There's 80% nitrogen in the air we're breathing right now. There's no nitrogen. So you avert the potential for nitrogen narcosis.
So nitrogen's not narcotic at one atmosphere, but you get something called the Martini effect.
Chapter 4: What role do exogenous ketones play in metabolic therapies?
And as you go down lower, nitrogen becomes narcotic. So that's something else that we study. So you're breathing 100% oxygen, and then there's a CO2 scrubber. So you're blowing out the exhaled carbon dioxide is scrubbed out from the breather, and it's a closed circuit. So there is no off-gassing associated with scuba diving or even other types of technical diving where you have some off gassing.
And the reason that they can do that is because you're not wasting gas on the 80% nitrogen. You basically store the CO2 that's coming out. Once you've scrubbed it, you've got pure O2 coming in. So your volume of air needed is much lower because you're just solving for the oxygen.
That's part of it because the oxygen tanks are pretty small with a rebreather, but it's analogous to, we have a couple of ponds on our property. And when I go in the pond and I see bubbles, Coming across the pond, I know an alligator is coming towards me.
When your brother was there, we were looking at the alligators and just getting them to come to us by throwing pebbles in there when they hear something. So if I go 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 still you can clearly see the bubble trail coming to you.
So with a closed circuit rebreather, that completely averts that, the bubble trail, and then there's also the noise that the bubbles make. So you don't have that. The problem is if you're wearing a closed circuit and you dive down to 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 going to have a seizure within five minutes. So oxygen is a stimulant. It stimulates a massive amount of glutamate release that activates AMPA receptors, NMDA receptors. It stimulates the neural network in ways. It also sort of deactivates or inhibits an enzyme, glutamic acid, acid decarboxylase, which converts more glutamate to GABA. 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 oxygen, which kind of has some people who study hyperbaric oxygen a little bit standoffish towards me. But in the context of lower oxygen, hyperbaric oxygen therapy can be very therapeutic.
I do want to talk about that. There's a lot I want to ask you about hyperbaric oxygen, but I want to finish the swing on this particular application. When was it clear to the Navy the problem that you described, which is when we have closed circuit rebreathers with 100% oxygen, we're running into problems with our divers. These problems are dramatic.
I mean, if you have a seizure at 100 feet, you're going to die pretty quickly. So when did they come to realize this? And was this a relatively recent discovery?
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Chapter 5: What are the implications of sodium and potassium in ketone salts?
Yeah. And I wanted to balance the sodium with potassium. So that was my original thing. I was like, I was going to create a ketone cell and just balance the sodium with potassium, but it wasn't there.
And are those covalently bound or not? Ionically bound.
You don't covalently? Yeah.
Yeah. Okay. So again, just- Sodium's positive? Trying to get everybody back to high school chemistry. You can either take this highly, highly acidic BHB molecule and you can covalently bind it through an ester to 1,3-butanediol, or you can say, let's be done with that baggage of the 1,3-butanediol and let's have a non-covalent, an ionic bound to a salt.
And I just need a positive charge to offset the negative charge. So then you were saying, okay, I want to do sodium because I can do a lot with it. And then tell me where the potassium comes in because you want sodium and potassium. Both of them are two positive charges instead of one calcium or one magnesium, which have two positive charges.
Yeah. So the idea is to have monovalent and divalent cations. You can spread the beta-hydroxybutyrate out to create like a quad salt was the idea back in 2011. So reaching out to Patrick, it wasn't in the CAST database. No one had thought about it. You couldn't buy it. So we had to make it. And then we made the calcium and the magnesium.
And through time, basically, we settled on a ratio of sodium, potassium to calcium, similar to Element. So they're kind of ahead. But Element is sodium chloride. So Ketostart, or from Audacious Nutrition, is sodium beta hydroxybutyrate and the calcium. And it's got a spread of electrolytes that are similar. So you're giving electrolytes and also giving ketones. And that's
really important when you start a ketogenic diet because you're replenishing the electrolytes that you are spilling out more through a natriuretic effect, especially the sodium. And also there's an energetic gap in the brain when you start a ketogenic diet where you have an energetic need for the increase in ketones.
We should go back to that, Dom, because I think a lot of people have lived that experience and they don't understand why, which is in the early stages of a ketogenic diet, 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.
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Chapter 6: How do exogenous ketones compare to traditional ketosis?
How much would you see an increase in you?
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 spiking in insulin. But if you consume it and you get above 1.5 to 2 millimolar, at least in me and a few other people that did this, then you see this counter-regulatory dump in insulin.
And that would also explain when people drink a large dose of 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 about two hours later or thereabouts, you can be hypoglycemic and also hypoketotic, which means your ketones come up, you utilize them as fuel,
Chapter 7: What is the role of hyperbaric oxygen therapy in cognitive enhancement?
But you've released insulin, and that caused peripheral glucose disposal. And then you get into a point where you're running, for example, and then you tank. And you could trigger a headache, as it does with me, if you take a large dose. So there's ways around that. But you're saying the salt... produces that effect much less?
The salt does not produce that effect at all for a number of different reasons. I think 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 in the packet, what's the brand that you brought for me? Audacious Nutrition Keto Start. Okay. So in that packet, you're getting about how many grams of electrolytes? About one gram total?
Chapter 8: How can ketogenic diets impact cancer and Alzheimer's treatment?
Yeah, total about one gram, like sodium, then calcium, magnesium, potassium. So there's different formulations. The packets are a little bit smaller, about the size of Element now. You're getting about 6 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, depending upon which packet you take, 6 grams or 10 grams of pure beta-hydroxybutyrate in the two different enantiomers. So that's another thing that we could talk about too.
Equal mix of R and D?
Yes, a 50-50 ratio of D and the L and R and S. 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. I'm not forgetting about acetone.
So when somebody my size, 180 pounds, 10 grams of BHB will take me to what level for how long? At rest, let's just say I'm not exercising.
For me, maybe we can include it in the show notes. I could show you my CKM, my continuous ketone monitor, and shoots me up for, I guess it's about four hours. One packet, four hours. But you're starting at a high level.
I'm at zero.
No. Well, I would eat carbohydrates to make sure I'm zero to start with. And I did it under, I've done this dozens of times, but it's interesting. If I'm sitting in my car and driving, I had a road trip and I drank it and I had my CKM on. It was elevated for like four to six hours and I was super hyper-focused driving and it was great.
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