#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.
Timestamps are as accurate as they can be but may be slightly off. We encourage you to listen to the full context.
Podcast Summary
Dom D'Agostino, a neuroscientist and metabolic therapy expert, shares cutting-edge insights into ketogenic diets and exogenous ketones on this comprehensive episode. (02:30) The discussion covers the evolution from his early Navy-funded research on oxygen toxicity to developing practical ketogenic strategies for both therapeutic and performance applications. D'Agostino explains the critical differences between nutritional ketosis (achieved through diet) and supplemental ketosis (using exogenous ketones), providing clear guidance on implementation, common mistakes, and optimal protocols. (15:00) The conversation explores emerging applications in cancer treatment, particularly glioblastoma, psychiatric disorders including anorexia, and neurodegenerative diseases like Alzheimer's. Additionally, the episode delves into hyperbaric oxygen therapy protocols for traumatic brain injury and cognitive enhancement, offering evidence-based recommendations for various clinical applications.
- Main Focus: Practical implementation of ketogenic therapies, exogenous ketone supplements, and their applications for metabolic health, cognitive enhancement, and therapeutic interventions
Speakers
Dom D'Agostino
Dom D'Agostino is a neuroscientist and professor at the University of South Florida who has become a leading authority on metabolic therapies, particularly ketogenic diets and exogenous ketones. His career began with Navy-funded research studying oxygen toxicity in military divers, which led him to discover the neuroprotective effects of ketosis. D'Agostino has authored numerous peer-reviewed publications and currently leads research on ketogenic interventions for cancer, neurological disorders, and military applications, while also serving as an advisor for several health technology companies.
Peter Attia
Peter Attia is a physician and longevity expert who hosts The Drive podcast, focusing on translating complex health science into actionable insights. He has extensive personal and clinical experience with ketogenic diets and metabolic interventions, having collaborated with D'Agostino for over a decade on various research projects. Attia brings a practical, evidence-based perspective to discussions about health optimization and therapeutic applications of metabolic strategies.
Key Takeaways
Track Your Ketone Levels and Macros for Success
D'Agostino emphasizes that the biggest mistake people make when attempting ketosis is failing to measure their actual ketone levels and track their food intake. (27:16) Without objective measurements, people often assume they're in ketosis when they're not, or fail to correlate their dietary choices with ketone production. He recommends using blood ketone meters (gold standard) or breath meters for accuracy, and tracking apps like Carbon to monitor macronutrient ratios and total calories. This data-driven approach allows you to understand what foods elevate or suppress your ketones, enabling you to optimize your approach rather than guessing.
Prioritize High Protein on Ketogenic Diets
Contrary to traditional ketogenic diet recommendations of 8-12% protein, D'Agostino advocates for 20-30% protein intake to preserve muscle mass and metabolic health. (38:35) For someone his size (220 pounds), this translates to potentially 220 grams of protein daily when very active. He learned through personal experience that restricting protein too severely led to significant muscle loss despite ketosis. Higher protein intake supports muscle preservation, provides greater satiety, and doesn't prevent ketosis when properly implemented with adequate fat and carbohydrate restriction.
Use Ketone Salts to Smooth Diet Transitions
Exogenous ketone salts can dramatically improve the transition into nutritional ketosis by bridging the "energetic gap" that occurs when glucose levels drop but ketone production hasn't fully ramped up. (63:57) D'Agostino explains that ketone salts combined with electrolytes (like his Keto Start product) provide both immediate ketone availability and replace the sodium, potassium, and other minerals lost during the early ketogenic transition. This prevents the brain fog, fatigue, and orthostatic hypotension that often derail people's ketogenic attempts, making adherence much more achievable.
Stay Within Optimal Ketone Ranges
Higher ketone levels are not necessarily better and can become dangerous above 2-3 millimolar, leading to "energy toxicity" and metabolic stress. (87:16) D'Agostino has observed that ketone levels above 2 millimolar can trigger counterregulatory insulin responses and potentially cause hypoglycemia, especially with rapid-acting ketone esters. The therapeutic sweet spot appears to be 0.5-2 millimolar, where you get the cognitive and metabolic benefits without the negative side effects. This is particularly important when using exogenous ketones, where it's easier to inadvertently push levels too high.
Consider Racemic Ketone Formulations
D'Agostino advocates for using racemic (50/50 D and L) beta-hydroxybutyrate rather than pure D-BHB because the L-form provides sustained, slower-metabolizing ketones with unique signaling benefits. (70:30) While D-BHB gets rapidly metabolized for energy, L-BHB hangs around longer in the brain and may provide important anti-inflammatory and epigenetic effects through pathways like NLRP3 inflammasome suppression. This creates both immediate fuel availability and longer-lasting therapeutic effects, making racemic formulations potentially superior for cognitive enhancement and neuroprotection.
Statistics & Facts
- Clinical ketosis is defined as blood beta-hydroxybutyrate levels above 0.5 millimoles per liter, with therapeutic benefits typically seen between 0.5-2 millimolar range. (17:14)
- In pediatric epilepsy, approximately two-thirds of drug-resistant patients respond therapeutically to ketogenic diets, with about one-third achieving complete seizure control (95-100% reduction). (22:31) Additionally, 10-15% become "super responders" who can eventually discontinue the diet while maintaining seizure freedom.
- There are currently 558 registered clinical trials studying ketogenic diets listed on clinicaltrials.gov, with 40-50 specifically focused on psychiatric disorders including bipolar, schizophrenia, major depression, anxiety, anorexia, and alcohol use disorders. (80:56)
