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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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View the Show Notes Page for This Episode

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Carole Hooven is a human evolutionary biologist whose research centers on testosterone, sex differences, and behavior. In this episode, she explores how prenatal testosterone orchestrates male development in the body and brain, how early hormonal surges shape lifelong behavioral tendencies, and what rare natural experiments—such as 5-alpha-reductase deficiency—reveal about the biology of sex differentiation. She discusses distinct male and female aggression styles through an evolutionary lens, how modern environments interact with ancient competitive drives, and the implications of attempting to suppress them. The conversation also covers testosterone across the lifespan, the role of hormone therapy in both men and women, and Carole's own experience after surgical menopause, culminating in a broader discussion of masculinity, cultural narratives, and the consequences of denying biological sex differences.

We discuss:

• How Carole became interested in exploring the biological and evolutionary roots of sex differences and the role of testosterone [2:30];
• How testosterone and other hormones influence sex differences in aggression and behavior across species [9:45];
• How chromosomes, the SRY gene, and early hormones direct embryonic sexual differentiation [12:15];
• A stark contrast of male social bonding compared to females, and evolutionary parallels in chimpanzees [19:30];
• How hormones like DHT shape sexual differentiation, and how 5⍺-reductase deficiency reveals the distinct roles of these hormones [22:45];
• How sex chromosomes and prenatal testosterone shape early brain development and explain sex differences in childhood behavior [31:30];
• How gamete differences shape reproductive strategies, energetic costs, and sex-specific behavior [42:30];
• How evolutionary biology shapes sex differences in play, aggression, and conflict resolution (and how modern environments and cultural messaging can disrupt those patterns) [49:00];
• Why males commit disproportionately more violent crime, and how cultural and environmental forces shape aggression [1:01:00];
• Why females evolved different behavioral strategies: nurturing, risk aversion, and the cultural norms that override biology [1:04:00];
• Whether male aggression is still necessary in modern society, why the underlying biological drives persist, and how modern society redirects these drives [1:06:30];
• How testosterone levels naturally shift to support fatherhood and caregiving [1:13:30];
• How testosterone shapes male mating strategies, and why long-term pair-bonding persists even when reproduction is no longer at stake [1:18:30];
• The distinct roles of estrogen in male development, mood, libido, and muscle [1:25:00];
• How evolution, health, lifestyle, and androgen receptor biology shape modern testosterone replacement therapy (TRT) [1:34:15];
• Carole's experience with hormone replacement therapy (HRT), and the risks associated with TRT in younger men [1:45:15];
• How Carole rebuilt after controversy: leaving academia and recommitting to scientific honesty [1:51:30,];
• Carole's next book: examining masculinity, cultural narratives, and the cost of denying biological sex differences [1:57:30]; and
• More.

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