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.
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We discuss:
Timestamps: There are two sets of timestamps associated with the topic list below. The first is audio (A), and the second is video (V). If you are listening to this podcast with the audio player on this page or in your favorite podcast player, please refer to the audio timestamps. If you are watching the video version on this page or YouTube, please refer to the video timestamps.
- Dom and Peter’s shared interest in ketosis, and Dom’s scientific journey [A: 2:30, V: 0:11];
- Dom’s work for the Navy on oxygen toxicity [A: 7:00, V: 5:40];
- Nutritional ketosis defined: physiology, biomarkers, and how fasting and diet generate therapeutic ketones [A: 15:00, V: 14:20];
- The historical roots of ketogenic diets in epilepsy treatment, and evidence showing ketones reduce seizure activity and strengthen brain resilience [A: 19:00, V: 18:58];
- Dom’s personal experience on the ketogenic diet: tracking macros, getting enough protein, and monitoring ketone levels [A: 24:15, V: 25:08];
- Using a ketogenic diet for weight loss: Dom’s guidance on protein, fiber, calorie tracking, lipid monitoring, and more [A: 31:00, V: 33:05];
- Protein on ketogenic diets: Dom’s rationale for higher intake and muscle preservation [A: 38:00, V: 41:02];
- Incorporating carbohydrates into keto: timing, high-fiber foods, and other considerations [A: 41:30, V: 44:56];
- The carnivore diet: whether carnivore eating induces ketosis, how it functions metabolically, and why it may help individuals with autoimmune conditions [A: 44:15, V: 48:21];
- Early exogenous ketones: how 1,3-butanediol works, its liver toxicity risk, and why ketone esters replaced it [A: 48:15, V: 53:10];
- The progression of exogenous ketones: why BHB monoesters and ketone salts emerged as better alternatives to 1,3-butanediol for ketone supplementation [A: 59:30, V: 1:06:31];
- Ketone salts: easing the transition into ketosis, dosing, and how they compare to ketone esters [A: 1:04:00, V: 1:11:46];
- The differences between D- and L-β-hydroxybutyrate, and how racemic mixtures may elevate ketones longer and offer unique biological effects [A: 1:09:30, V: 1:18:06];
- How ketosis may boost NAD, and why NAD supplements have fallen short so far [A: 1:16:30, V: 1:25:54];
- Emerging evidence for using a ketogenic diet to treat anorexia and other psychiatric disorders [A: 1:20:30, V: 1:30:34];
- Potential cognitive and performance benefits of ketone supplementation, and why pushing ketones too high can be dangerous [A: 1:23:45, V: 1:34:18];
- Applications for ketone esters, and why ketone salts or MCT-blended formulations may be safer and more practical for most people [A: 1:29:15, V: 1:40:25];
- The role of a ketogenic diet in treating cancer [A: 1:34:45, V: 1:46:37];
- The potential of a ketogenic diet for treating Alzheimer’s disease [A: 1:45:45, V: 1:59:31];
- Tools for cognitive enhancement: ketones, alpha-GPC, MCT, caffeine, strategic fasting, and more [A: 1:53:45, V: 2:09:45];
- Hyperbaric oxygen therapy for concussion, TBI, PTSD, and cognitive function, including protocols and dosing approaches [A: 1:55:30, V: 2:11:26];
- Peter’s takeaways, recommended products, and additional resources to learn more [A: 2:03:00, V: 2:20:30]; and
- More.
Show Notes
Dom and Peter’s shared interest in ketosis, and Dom’s scientific journey [A: 2:30, V: 0:11]
- It’s been a long time since Peter has seen Dom in person
- Dom sees Peter’s brother (Paul) a lot more
- Paul’s an amazing entrepreneurial mentor and a life mentor
- Dom has been on this podcast a couple of times
- We’ve probably got hundreds of thousands of listeners today that weren’t listeners the first and second time he was on the podcast
- And for those that were, it would be understandable that they’ve forgotten most of what we’ve spoken about
Just by way of background, Peter explains how he and Dom are connected
- Ken Ford connected them back in 2011-ish
- At the time, Peter was about a year into experimenting with a ketogenic diet
- Having all sorts of interesting success with it for the most part ‒ once he got over the hump of figuring out how to do it
- We must have connected at his institute, and then the rest is kind of history
- We then, through our friendship became very deeply involved in the testing of the earliest generations of 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
How Dom’s interest in this space came to be
- Peter recalls that Dom’s Ph.D. was in neuroscience
- Yeah, nutrition
- He started doing an undergraduate thesis project in neuroscience and the neural control of autonomic regulation
- Specifically the brain network, the rostral ventrolateral medulla
- This is the brain stem network that controls respiration ‒ inspiratory neurons, expiratory neurons, and how they respond to oxygen and CO2
- And that led him down the path of oxygen, hypoxia, hyperoxia, hypercapnia, extreme environments
- What happens to the brain under oxygen deprivation and nutrient deprivation
- At the time, he was interested in alpha-L-Polylactate because it was in Cytomax, which was something he used because he raced mountain bikes
- Dom was testing some things lactate, and then he got steered onto the ketogenic diet after getting 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
Dom was mostly interested in drugs, but then he pivoted and went back to the ketogenic diet because it works for so many different seizure disorders when drugs fail
- He was gravitating towards a tenure track position, and everybody told him this was the dumbest thing to do
- You can’t get NIH funding with ketogenic, nobody had heard of the ketogenic diet
- This was around 2005
- Dom started tinkering with ketones
- In 2007 he started writing grants, and in 2008 he got a postdoctoral grant
- It was very sizable ‒ like a NIH-level grant and it paid full indirects
- That came from the Office of Navy Research (part of the Department of Defense)
- His position went from postdoc to something called a Research Assistant Professor
- Which is like an intermediate position before you get into tenure track
- The university was gauging his productivity
- Dom got good data on hyperbaric atomic force microscopy, very mechanistic research
- He also did patch clamp electrophysiology and confocal microscopy
His work was really focused on redox mechanisms and looking at superoxide production under graded levels of oxygen and different metabolites
- In the process of doing all that, he had no interest in cancer, but he had some glioblastoma cells and he threw them into the hyperbaric chamber
- And under confocal microscopy, he could see the mitochondria were lighting up and then kind of exploding or disappearing in the cancer cells
- That was kind of unique, and that led him on a side tangent thing to study cancer
- But the central thing that he studied was neuroscience
- He’s been in the neuroscience department and mainly focused on that
Dom’s work for the Navy on oxygen toxicity [A: 7:00, V: 5:40]
The problem with too much oxygen and Dom’s work for the Navy
- Folks might not understand why the navy would be interested in the effects of too much oxygen
- When you think of the navy, you think of being underwater
- When you think of being underwater, you think of oxygen deprivation
What is it about certain types of diving that actually bring about the opposite problem?
- 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 3.0 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 what oxygen toxicity is
How does a rebreather work?
What is the concentration of oxygen they’re breathing in?
- A closed circuit rebreather, for example, like a Drӓger rebreather, those early rebreathers and even now it’s high concentration
You’re breathing 100% oxygen, so there’s no nitrogen
- There’s 80% nitrogen in the air we’re right now
- There’s no nitrogen [in a rebreather] so you avert the potential for nitrogen narcosis
- So nitrogen is not narcotic at one atmosphere, but you get something called the Martini effect
- As you go down lower, nitrogen becomes narcotic (that’s something else that Dom studies)
- 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
- Peter adds the reason 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
- Dom explains that the oxygen tanks are pretty small [that are used] with a rebreather
Analogy to understand why the Navy uses a rebreather
{end of show notes preview}
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Dominic D’Agostino, Ph.D.
Dominic “Dom” D’Agostino earned a BS in Biological Sciences and Nutrition Science from Rutgers University then completed his Ph.D. in Neuroscience at the University of Medicine and Dentistry of New Jersey. Dr. D’Agostino completed postdoctoral research with Dr. Jay B. Dean in the Department of Neuroscience, Cell Biology and Physiology at Wright State University Boonshoft School of Medicine in Dayton, OH. He was also a postdoctoral fellow in the department of Molecular Pharmacology and Physiology at the University of South Florida (USF) Morsani College of Medicine in Tampa, FL. He continued at USF as an Assistant Professor and is and currently is a tenured Associate Professor in the Department of Molecular Pharmacology and Physiology at the USF Morsani College of Medicine. Dr. D’Agostino is also a Senior Visiting Research Scientist at the Institute for Human and Machine Cognition (IHMC).
Dr. D’Agostino’s laboratory develops and tests metabolic-based strategies for targeting CNS oxygen toxicity (seizures), epilepsy, neurodegenerative diseases, and cancer. The main focus of his lab over the last 10 years has been understanding the anticonvulsant and neuroprotective mechanism of the ketogenic diet and ketone metabolite supplementation. The shift in brain metabolism (from glucose to ketones) reduces neuronal hyperexcitability, oxidative stress and enhances brain energy metabolism. This approach can be used to treat a wide variety of pathologies linked pathophysiologically to metabolic dysregulation, including cancer. Other areas of interest include researching drugs that target cancer-specific metabolic pathways. He was a research investigator and crew member on NASA’s Extreme Environment Mission Operation (NEEMO 22) and has a personal interest in environmental medicine and methods to enhance safety and physiological resilience in extreme environments. His research is supported by the Office of Naval Research (ONR), Department of Defense (DoD), private organizations and foundations. [KetoNutrition]
Facebook: Dominic D’Agostino
Instagram: dominic.dagostino.kt
LinkedIn: Dominic D’Agostino
Podcast: The Metabolic Link (on YouTube)
Website: Dominic D’Agostino and KetoNutrition
