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Peter Attia and Dom D’Agostino explore the science, promise, and caveats of ketosis as a therapeutic and performance strategy. They trace Dom’s trajectory from neuroscience and naval research into the ketogenic space, detailing how high-oxygen environments, hyperbaric oxygen exposure, and redox biology illuminate brain energetics and seizure mechanisms. The conversation moves from foundational ketosis biology—how fasting, carbohydrate restriction, and beta-hydroxybutyrate shift brain fuel and gene regulation—to practical optimization: tracking ketones, proteins, and calories for athletes, the role of ketone esters versus ketone salts, and the need to balance electrolytes to prevent dehydration and dizziness during the transition to ketosis. They emphasize that nutritional ketosis is a metabolic therapy with pleiotropic effects, including neuroprotective signaling and anti-inflammatory potential, rather than a simple weight-loss protocol, and they stress individualized approaches guided by biomarkers and blood work. The discussion then broadens to exogenous ketones as a bridge and tool, addressing pharmacokinetics, enantiomers, and the tradeoffs of different formulations. They compare monoesters, diesters, and salts, explain the D- versus L- beta-hydroxybutyrate dynamics, and reveal how mixing ketones with MCTs or other compounds can modulate absorption, insulin response, and brain energy delivery. Dom candidly shares experimental cautions about liver load, energy toxicity, and the importance of dosing strategies that avoid insulin spikes while maintaining a stable 1–2 millimolar ketone range for cognitive and physical work. The pair also dives into applications for cancer and brain disorders, outlining a framework for glioblastoma and the glucose-ketone index, and they discuss how metabolic therapy could complement standard-of-care options while acknowledging the current absence of definitive randomized trials for many cancers and neurodegenerative diseases. They close with candid reflections on ongoing clinical research, regulatory hurdles, and the hope that metabolic approaches—together with targeted drugs and immune therapies—could meaningfully extend survival and improve quality of life in difficult conditions like GBM and Alzheimer’s disease.

Ketones function by opening escape valves in the body, leading to calorie wastage rather than efficient fat burning, which is key to weight loss. Steven Gundry's book, "Unlocking the Keto Code," presents keto as a longevity strategy, revealing that ketones are not an ideal fuel source. Research shows that while muscles initially prefer ketones during starvation, they soon switch to free fatty acids. Even in full ketosis, only a portion of energy needs are met by ketones, raising questions about their efficiency. The ketogenic diet, originally developed for epilepsy treatment, involves high fat intake and low carbohydrates, but many struggle to maintain it long-term. Gundry highlights that metabolic inflexibility affects many Americans, making it hard to enter ketosis. He shares a case of a patient who gained weight on a ketogenic diet due to insulin resistance, challenging the misconception that keto guarantees weight loss. Gundry emphasizes that a ketogenic diet can lead to inefficient fat burning, likening it to a Ferrari wasting fuel. He advocates for a balanced approach, incorporating fiber-rich and polyphenol-laden foods to support gut health and mitochondrial function. He discusses the importance of postbiotics and the role of gut bacteria in overall health. Ultimately, Gundry suggests a flexible dietary pattern that includes healthy fats, fiber, and polyphenols while avoiding processed foods and excess sugar. He underscores the significance of metabolic flexibility and the benefits of intermittent fasting to enhance ketone production and promote weight loss.

Ketones aren’t a flavor of the month; they’re a metabolic lens, and this episode makes the case that metabolic health underpins most chronic disease. Dr. Andrew Koutnik, a research scientist who has studied metabolic health and the keto diet, explains that his mission is to empower people to control their health by translating science into action. After a difficult childhood with obesity and multiple chronic diagnoses, he embraced the ketogenic diet and documented its effects on diabetes, obesity, and even neurological conditions. He wears an insulin pump and a continuous glucose monitor to guide his own management, illustrating how glucose control sits atop a pyramid of risk factors. HbA1c, a two-to-three-month average, is identified as the strongest predictor of future complications, and carbohydrates are described as the most potent driver of glucose fluctuations. On keto, carbohydrates are restricted, fat becomes the primary energy source, and ketone bodies become a major fuel for the brain and muscles. The host and guest discuss the longest study of its kind—a ten-year, controlled look at a person with type 1 diabetes who switched from a standard ADA-style diet to ketogenic eating. LDL cholesterol nearly doubled, yet glycemic control remained normal and insulin requirements dropped by about 40%. A broader analysis of 46,000 type 1 diabetes patients found that many could normalize glucose with very low-carb approaches. The conversation also covers cognitive and psychiatric implications of ketosis, including improved brain network stability with exogenous ketones, reduced inflammation, and potential protection against cognitive decline and some forms of cancer progression. They describe how athletes can achieve high fat oxidation with sufficient adaptation, sustaining high-intensity exercise on keto. Beyond theory, practical guidance centers on food choices and daily habits. They warn against liquid calories and foods with high glycemic loads—white bread, white rice, potatoes, cereals, and many fruits when not carefully chosen. They emphasize “therapeutic carbohydrate restriction” for those with metabolic disease and note that about 93% of Americans have some metabolic derangement. Core habits—regular exercise, adequate protein, sufficient calories, and good sleep—are presented as foundation stones. The discussion also highlights the challenge of interpreting nutrition science and the reality of individual variation, underscoring that personal experimentation can reveal what works. The overarching message is that metabolic health is attainable through diet and lifestyle, with ketosis and ketone therapies offering potent tools.

In this episode of The Diary of a CEO, Steven Bartlett welcomes Benjamin Bikman, a leading metabolic scientist, to dissect how insulin orchestrates weight gain and how carbohydrate restriction and ketosis can reshape energy balance. The guest dispels the oversimplified “eat less, move more” paradigm, arguing that insulin’s role in energy storage is the pivotal lever for fat loss. He explains that two variables drive fat loss: shrinking fat cells and lowering insulin by reducing carbohydrate intake. The discussion traverses how insulin spikes suppress the brain’s access to energy from glucose and ketones, triggering hunger even when fat stores are plentiful. Bikman emphasizes that fat loss should come from protocols that minimize hunger and energy scarcity, highlighting that meals with the same calorie count but different macronutrient compositions yield different metabolic rates due to insulin’s regulation of energy use. He connects ketosis not only to fat burning but to diverse brain benefits, including reduced anxiety and improved attention, and shares how ketones serve as both fuel and signaling molecules that influence blood vessel dilation and brain chemistry. The conversation moves from practical diet design—structured indulgences around carb-rich holidays, prioritizing protein and fat to keep insulin low, and leveraging exogenous ketones during transitions—to the nuance of insulin’s supremacy in fat metabolism, illustrated with clinical anecdotes about type 1 diabetes and insulinoma to underscore how insulin control shapes outcomes. The host and guest explore the potential of breastfeeding-like clarity in patient education while acknowledging the complexities of real-world adherence, social media scrutiny, and evolving scientific discourse. Bikman also delves into the therapeutic potential of ketones for neurological and cardiovascular health, the role of exogenous ketones in preserving lean mass during weight loss, and the possibility of using GLP-1 therapies in a cycle with low-carb coaching to sustain long-term changes. They close with practical daily frameworks, including fasting, big lunch planning, regular resistance training, sleep optimization, and the impact of stress and testosterone on metabolic health, offering a holistic blueprint for listeners seeking a healthier 2026.

In this episode of The Diary of a CEO, Steven Bartlett chats with Dr. Benjamin Bikman about the science of weight, metabolism, and the practical strategies that can help people lose fat without feeling constantly hungry. The conversation centers on insulin as a master regulator of energy storage, arguing that the traditional calories-in, calories-out mindset oversimplifies the body’s complex hormonal control of weight. Bikman argues that lowering insulin through reduced carbohydrate intake shifts the body toward burning fat and producing ketones, which become a steady brain fuel and a signal that can modulate hunger, mood, and cognitive performance. He emphasizes that sustainable fat loss hinges on two variables: shrinking fat cells and managing insulin, rather than merely cutting calories. The discussion covers real-world implications, including how to structure meals, harness ketosis, and deploy exogenous ketones to ease the transition. In addressing common concerns, Bikman addresses the sustainability of ketogenic eating, the brain’s reliance on ketones, and the potential cognitive and mood benefits of stabilizing energy sources. He explains how ketones act as both fuel and signaling molecules that improve brain energy, mood, and even blood vessel function, which can have downstream effects on blood pressure and cognitive health. The dialogue also examines individual differences, such as sex hormones and the luteal phase in women, and how these nuances affect fat burning, cravings, and insulin sensitivity. The host and guest discuss practical routines—fasting windows, protein- and fat-forward meals, resistance training, and even supplements like omega-3s, creatine, and collagen—that can support weight management without imposing harsh hunger. They also explore the role of wearables and CGMs in providing actionable feedback, the potential dangers of insulinoma and the limits of GLP-1–based therapies, and the need to approach medical claims with humility and scientific scrutiny. The episode ultimately blends rigorous metabolic science with candid, personal storytelling about health goals, family life, and longevity. It underlines the value of having a strong why and a realistic plan that minimizes hunger while optimizing insulin dynamics, ketone production, and energy throughout the day. The rich discussion invites listeners to rethink weight loss strategies, consider individualized nutrient timing, and leverage emerging tools and lifestyle choices to pursue a healthier 2026 without relying solely on restrictive dieting or one-size-fits-all prescriptions.

In this episode of the Tim Ferriss Show, Tim interviews Dr. Dominic D'Agostino, an assistant professor at the University of South Florida and a senior research scientist at the Institute for Human and Machine Cognition. Dom specializes in nutritional neuroscience, focusing on metabolic therapies, particularly ketogenic diets and fasting. He has fasted for seven days and still managed to deadlift 500 pounds for ten reps, showcasing his physical and intellectual prowess. Dom's research primarily involves developing and testing metabolic therapies, including ketogenic diets and ketone supplements, to induce nutritional and therapeutic ketosis. His work has been funded by various government agencies, including the Department of Defense. The discussion touches on cutting-edge research related to cancer prevention, longevity, and performance enhancement. Dom explains that ketosis occurs when the body uses fat as its primary energy source instead of carbohydrates, leading to the production of ketones. He emphasizes the benefits of ketosis for brain health, metabolic efficiency, and muscle preservation. Dom also discusses the anti-catabolic effects of ketones, which can help maintain muscle mass during caloric restriction. The conversation delves into the implications of fasting and nutritional ketosis for neurodegenerative diseases like Alzheimer's and Parkinson's. Dom suggests that fasting may help mitigate the onset of these diseases by reducing inflammation and promoting cellular repair. He highlights the importance of medical supervision when fasting, especially for individuals with existing health conditions. Dom shares insights from his research on advanced lifters following a ketogenic diet, noting that they maintained or increased strength and muscle hypertrophy while losing fat. He explains that insulin sensitivity can improve with a ketogenic diet, which may lead to better performance outcomes for older athletes. The episode also covers the potential of exogenous ketones to mimic the benefits of fasting and enhance athletic performance. Dom discusses the safety of exogenous ketones, citing studies that show no significant toxicity at high doses in animal models. He emphasizes the importance of dietary fat sources and the role of fiber in promoting ketosis. Tim and Dom explore the practical aspects of a ketogenic diet, including meal composition and the benefits of intermittent fasting. Dom shares his personal dietary habits, which include high-fat meals with fish, eggs, and green vegetables, and a unique dessert made from sour cream and dark chocolate. In rapid-fire questions, Dom recommends resources for those interested in ketosis, including the website ketogenicdietresource.com and books like "Cancer as a Metabolic Disease" by Tom Seyfried. He concludes by discussing the potential of ketosis to aid in repairing mitochondrial damage and its relevance to conditions like Lyme disease. Overall, the episode provides a comprehensive overview of the science behind ketosis, its applications in health and performance, and practical tips for implementing a ketogenic lifestyle.

The episode delves into ketosis as a tool for weight loss, mood stabilization, cognition, and potential neuroprotection, with Dr. Dom D’Agostino offering a practical, experience-based tour of how ketogenic fasting regimens influence brain chemistry and systemic metabolism. The conversation begins by outlining how ketosis shifts energy substrate use from glucose to fat-derived ketones, highlighting the diuretic and natriuretic effects that can lower blood pressure and fluid volume while reducing insulin resistance. The hosts discuss the brain’s response to ketones, including elevated GABA, dampened glutamate activity, and a resulting calming effect that underpins mood stabilization and seizure control. The discussion broadens to therapeutic contexts, including metabolic psychiatry and cancer care, where ketosis may slow glycolysis-tethered tumor growth and improve treatment responses. The speakers emphasize that ketosis is not a cure but a metabolic modulator with widespread effects—from anti-inflammatory actions to immune modulation and potential benefits for neurodegenerative risk factors. They also explore how intermittent fasting and metabolic memory may create lasting improvements in mitochondrial function, insulin sensitivity, and fat oxidation, suggesting a persistent “metabolic memory” that can persist beyond active dietary change. Throughout, the hosts address practicalities of following a ketogenic lifestyle: meal composition, macro balance, and strategies to minimize gluconeogenesis while preserving muscle. They discuss exogenous ketones, including monoesters and diesters, weighing palatability, pharmacokinetics, toxicity, and the risks of chronic high-dose use, particularly with 1,3-butanediol-based formulations. Close attention is paid to real-world monitoring tools such as CGMs and ketone meters, plus the importance of fiber, fat, and electrolyte management to sustain ketosis during meals. The broader message is that ketogenic strategies—when thoughtfully applied and personalized—can be powerful tools in improving brain function, mood, and longevity, albeit with careful consideration of dosage, timing, and individual physiology.

In this episode of The Diary of a CEO, Dr. Annette Bosworth joins host Steven Bartlett to unpack how insulin, ketones, and a ketogenic lifestyle influence brain health and aging, including the potential links to dementia and cognitive decline. The conversation centers on insulin as a chronic disease driver when levels stay chronically high, promoting weight gain, inflammation, and “trash” in the brain and body. Bosworth emphasizes practical changes to reduce insulin, notably moving calories to earlier in the day, minimizing late-night eating, and adopting a fat-forward, very low-carbohydrate approach that provokes ketone production. She explains that insulin resistance creates a metabolic environment where the body preferentially stores sugar as glycogen or fat, making it difficult to switch to fat-derived ketones even during fasting. The dialogue pivots to how ketones can act as a cleaner, more efficient fuel for brain cells, potentially slowing or altering the trajectory of neurodegenerative conditions like Alzheimer’s, though she cautions that long-term causality remains unsettled and that results vary among individuals. A running theme is the difference between short-term dieting and a sustainable, medically supervised ketogenic strategy—referred to as the Keto Continuum—which outlines steps from initial carbohydrate reduction to extended fasting windows and strategic meal timing. Throughout, Bosworth shares clinical anecdotes, including dramatic stories of weight loss, improved energy, sharper cognition, and even apparent reversal of gray hair in some patients, all attributed to reduced insulin and higher ketone availability. She also discusses the role of the gut-brain axis, noting that fat-rich diets influence gut microbes and metabolites like butyrate that can modulate GLP-1 signaling and appetite. The interview weaves in personal experiences, such as Bosworth’s 21-day course and a 100-day sardine challenge intended to drive a deep metabolic reset, while addressing common concerns about sustainability, social life, gender differences, and the interaction of diet with medications like GLP-1 agonists. The episode ends with reflections on motivation, crisis-to-growth mental models, and Bosworth’s broader message: when insulin resistance is lowered and ketones are regularly produced, people can experience clearer thinking, steadier energy, and a higher quality of life, even as they navigate complex health challenges and life’s inevitable obstacles.