#375 - Ketogenic diet, ketosis & hyperbaric oxygen: metabolic therapies for weight loss, cognition, Alzheimer's & more | Dom D'Agostino, Ph.D.
Episode
128 min
Read time
2 min
Topics
Health & Wellness, Fundraising & VC, Leadership
AI-Generated Summary
Key Takeaways
- ✓Ketogenic Diet Efficacy for Epilepsy: Two-thirds of pediatric epilepsy patients who fail multiple drug therapies respond therapeutically to ketogenic diets, with one-third achieving complete seizure control. Ten to fifteen percent become super responders who maintain seizure freedom even after discontinuing the diet, suggesting curative potential through network stabilization.
- ✓Protein Requirements on Keto: Modified ketogenic diets should contain twenty to thirty percent protein rather than the historical eight to twelve percent. For active individuals, this translates to approximately one gram per pound of body weight to prevent muscle loss and sarcopenia, especially critical after age fifty when muscle turnover accelerates significantly.
- ✓Ketone Esters versus Salts: Ketone salts provide sustained elevation for four to six hours without insulin spikes when keeping blood levels under two millimolar. Ketone esters cause rapid rises that trigger counter-regulatory insulin release and potential hypoglycemia two hours post-consumption, making salts preferable for most applications outside acute medical interventions.
- ✓D versus L Enantiomers: Racemic beta-hydroxybutyrate contains fifty percent D-enantiomer metabolized rapidly for energy and fifty percent L-enantiomer metabolized three to four times slower. The L form provides sustained signaling effects including NLRP3 inflammasome suppression and epigenetic modifications while D provides immediate fuel, creating complementary therapeutic benefits.
- ✓Electrolyte Management During Transition: Ketogenic diets cause natriuretic and diuretic effects leading to sodium depletion and orthostatic hypotension. Consuming ketone salts bound to sodium, potassium, calcium, and magnesium during the first four to six weeks prevents brain fog and smooths adaptation by replacing lost electrolytes while bridging the energetic gap.
What It Covers
Dom D'Agostino discusses ketogenic diets, exogenous ketones, and hyperbaric oxygen as metabolic therapies. Topics include achieving nutritional ketosis, managing electrolytes during transition, differences between ketone salts versus esters, applications for epilepsy and cancer, and carnivore diets as ketogenic variants.
Key Questions Answered
- •Ketogenic Diet Efficacy for Epilepsy: Two-thirds of pediatric epilepsy patients who fail multiple drug therapies respond therapeutically to ketogenic diets, with one-third achieving complete seizure control. Ten to fifteen percent become super responders who maintain seizure freedom even after discontinuing the diet, suggesting curative potential through network stabilization.
- •Protein Requirements on Keto: Modified ketogenic diets should contain twenty to thirty percent protein rather than the historical eight to twelve percent. For active individuals, this translates to approximately one gram per pound of body weight to prevent muscle loss and sarcopenia, especially critical after age fifty when muscle turnover accelerates significantly.
- •Ketone Esters versus Salts: Ketone salts provide sustained elevation for four to six hours without insulin spikes when keeping blood levels under two millimolar. Ketone esters cause rapid rises that trigger counter-regulatory insulin release and potential hypoglycemia two hours post-consumption, making salts preferable for most applications outside acute medical interventions.
- •D versus L Enantiomers: Racemic beta-hydroxybutyrate contains fifty percent D-enantiomer metabolized rapidly for energy and fifty percent L-enantiomer metabolized three to four times slower. The L form provides sustained signaling effects including NLRP3 inflammasome suppression and epigenetic modifications while D provides immediate fuel, creating complementary therapeutic benefits.
- •Electrolyte Management During Transition: Ketogenic diets cause natriuretic and diuretic effects leading to sodium depletion and orthostatic hypotension. Consuming ketone salts bound to sodium, potassium, calcium, and magnesium during the first four to six weeks prevents brain fog and smooths adaptation by replacing lost electrolytes while bridging the energetic gap.
Notable Moment
D'Agostino reveals that pure D-beta-hydroxybutyrate monoester actually trended toward making seizures occur faster in animal models rather than preventing them. Only when combining beta-hydroxybutyrate with acetoacetate in one-to-one ratios to create redox balance did they achieve seizure control, fundamentally changing their research direction toward racemic formulations.
Episode Transcript
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. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members. And in return, we offer exclusive member only content and benefits above and beyond what is available for free. 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 the 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, one three 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 the podcast a couple of times, but I know that in podcast …
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