375 - The ketogenic diet, ketosis, and hyperbaric oxygen: weight loss, cognition, cancer, and more
Peter Attia interviews Dom D'Agostino, a neuroscientist and ketone researcher, on the mechanisms and applications of nutritional ketosis, exogenous ketones, and hyperbaric oxygen therapy. The conversation covers why the ketogenic diet works for drug-resistant seizures, how different ketone supplements compare biochemically, and emerging clinical research on ketosis for cognitive enhancement, weight loss, and cancer management. D'Agostino explains the critical differences between ketone salts, ketone esters, and 1,3-butanediol, and reveals why most people's ketogenic diet attempts fail due to tracking errors and protein miscalculation.
Key takeaways
- • Nutritional ketosis (blood BHB >0.5 mmol/L) is the only diet with an objective biomarker, and two-thirds of drug-resistant pediatric epilepsy patients achieve seizure control through the ketogenic diet, with some showing complete remission and becoming "super-responders" who maintain seizure freedom after discontinuation.
- • The most common mistake when starting a ketogenic diet is not tracking food intake or blood ketone levels; most people underestimate calories by 25-50% due to fat's high caloric density, making caloric restriction the primary driver of weight loss.
- • High-protein ketogenic diets (20-30% of calories from protein, or ~0.8-1g per pound of body weight) outperform traditional low-protein versions for muscle preservation, metabolic rate, and adherence, contradicting outdated RDA recommendations.
- • Ketone salts (particularly sodium/potassium/calcium/magnesium BHB) are superior to ketone esters for practical use because they do not trigger insulin spikes, cause fewer gastrointestinal issues, and effectively bridge the "energetic gap" during the first 1-2 weeks of ketogenic adaptation without the liver toxicity risk of 1,3-butanediol.
- • 1,3-butanediol is a powerful ketone precursor but carries dose-dependent hepatotoxicity (can double liver enzymes) and intoxicating effects; it was originally developed by NASA for long-duration spaceflight as a food preservative, making it inappropriate for elderly or frail populations despite its glucose-lowering effects.
- • The carnivore diet functions as a ketogenic diet when sufficiently high in fat, and emerging clinical data from Paleo Medicina in Budapest show therapeutic benefits for autoimmune disorders, type 1 diabetes, and cancer, though anecdotal reports from influencers may create selection bias in perception.
- • Continuous ketone monitors (like Sai Bio) now provide real-time interstitial BHB tracking comparable to CGMs, enabling precise dose optimization of exogenous ketones; D'Agostino's device shows accuracy within the first week but underestimates by ~50% by week two.
Recommendations (13)
"I use a coffee creamer called Keto Brains. It's like alpha GPC, MCT, theanine has a couple. It's a mixture of combinations of things."
Peter Attia · ▶ 1:44:46
"I got the little Cardio Chek meter which was super expensive at the time. I would say 2009 I started actually checking ketones"
Peter Attia · ▶ 25:15
"I got that later. I don't even think that might have been out yet, but I got that soon after because the Cardio Chek actually did like your HDL and like triglycerides"
Peter Attia · ▶ 25:30
"there's Advanced Ketogenic Therapies and it's a team of people and it's kind of spearheaded by Denise Potter. She's a registered dietitian"
Peter Attia · ▶ 36:01
"Audacious Nutrition Keto Start. You're getting about 6 to 10 grams of pure beta hydroxybutyrate minus the electrolytes."
Peter Attia · ▶ 1:19:19
"For me, maybe we can include it in the show notes. I could show you my continuous ketone monitor, and shoots me up for I guess it's about 4 hours."
Peter Attia · ▶ 1:17:01
"What were we doing with our Abbott finger sticks? Measuring D beta hydroxybutyrate."
Peter Attia · ▶ 1:18:07
"You can use an SGLT2 inhibitor, you can use I mean we have about two dozen different drugs that you could use."
Peter Attia · ▶ 1:51:50
Mentioned (6)
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