Esters versus salts: biochemistry and pharmacokinetics

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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.

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