375 - The ketogenic diet, ketosis, and hyperbaric oxygen: weight loss, cognition, cancer, and more
Peter Attia MDKey Moments
Ketogenic diet, ketones, and hyperbaric oxygen explored for health, cognition, cancer, and weight loss.
Key Insights
The ketogenic diet, primarily high-fat, can be prescribed as a metabolic therapy with objective biomarkers like beta-hydroxybutyrate (BHB).
Ketogenic diets have shown significant efficacy for drug-resistant epilepsy, particularly in children, and are being investigated for cancer and neurodegenerative diseases.
Exogenous ketones (salts and esters) offer an alternative to strict dietary ketosis, potentially bridging metabolic gaps, aiding cognitive function, and mitigating ketogenic diet side effects.
While 1,3-butanediol and ketone esters can elevate BHB, they may come with risks like liver toxicity and narcotic effects, prompting advancements in safer formulations like ketone salts.
Hyperbaric oxygen therapy (HBOT) shows promise for acute concussion and TBI, with ongoing rigorous research exploring its broader neuroregenerative and cognitive benefits.
Research into NAD+ shows potential for stabilizing the molecule and its application in conditions involving metabolic stress, aging, and neurological disorders, though clinical translation is challenging.
THE NEUROSCIENCE ROOTS OF KETOGENIC THERAPIES
Dr. Dom D'Agostino's interest in ketones stems from his neuroscience background, initially focusing on oxygen toxicity and neural regulation. His research pivoted to the ketogenic diet due to its profound effects on seizure disorders when drugs failed. This early work, supported by military grants, provided him with the tools and funding to explore mechanisms of oxygen toxicity and, serendipitously, cancer cell responses to hyperbaric conditions.
UNDERSTANDING NUTRITIONAL KETOSIS AND METABOLIC SHIFTS
Ketosis is achieved by suppressing insulin, mobilizing fatty acids, and converting them into ketone bodies (BHB and acetoacetate) for brain fuel. Nutritional ketosis, derived from a carbohydrate-restricted ketogenic diet (typically 60-70% fat), is the most researched form. A key biomarker, BHB above 0.5 mmol/L, defines this state, which profoundly alters metabolic physiology and brain neuropharmacology, offering pleiotropic benefits beyond mere weight loss.
THE THERAPEUTIC POTENTIAL OF KETOGENESIS
Historically, fasting was recognized for controlling seizures, leading to the widespread use of ketogenic diets to manage drug-resistant epilepsy, particularly in children, where it shows remarkable efficacy. Beyond epilepsy, research is rapidly expanding into its applications for cancer, metabolic diseases, and psychiatric disorders, with ongoing clinical trials investigating its role as an adjunct therapy.
NAVIGATING THE WORLD OF EXOGENOUS KETONES
Exogenous ketones, including salts and esters, offer a way to increase blood ketone levels without strict dietary adherence. While early forms like 1,3-butanediol and ketone esters had potential benefits, they also carried risks like liver toxicity and narcotic effects. Advancements have led to ketone salts, which provide a more stable and safer elevation of BHB with fewer side effects, making them useful for mitigating ketogenic diet transitions and potentially enhancing cognitive function.
THE PROMISE OF HYPERBARIC OXYGEN THERAPY (HBOT)
Despite limited FDA approvals, HBOT is showing promise for conditions like acute concussion and traumatic brain injury (TBI). Rigorous studies, including large-scale DoD-funded projects, are investigating its potential for neuroregeneration, improved cognitive function, and mental health benefits, even for veterans with past brain injuries. While protocols vary, early data suggests potential positive outcomes, though more controlled research is needed.
KETOGENIC STRATEGIES FOR CANCER AND NEURODEGENERATION
For aggressive cancers like glioblastoma, ketogenic therapy isn't a cure but can be a vital adjunct, potentially doubling or tripling survival by starving cancer cells of glucose and glutamine while boosting ketones. Similarly, for Alzheimer's and dementia, ketogenic interventions may combat the hallmark glucose hypometabolism and neuroinflammation. Patient selection, focusing on those with metabolic deficits, is crucial for maximizing therapeutic benefits.
OPTIMIZING KETONE INTAKE AND MITIGATING RISKS
Achieving therapeutic ketosis requires tracking macros, calories, and blood ketone levels. Common mistakes include underestimating intake and improper dietary formulation. For weight loss, a high-protein, high-fiber, moderate-fat approach is recommended. While exogenous ketones can offer benefits, maintaining blood ketone levels between 1-3 mmol/L is crucial to avoid energy toxicity and potential adverse insulin responses. Formulations like ketone salts offer a safer, more palatable way to achieve this.
THE EMERGING ROLE OF NAD+ AND FORMULATION SCIENCE
NAD+ is a central player in cellular energy metabolism affected by aging and stress. Stabilized NAD+ precursors are under investigation for various conditions, including neurological disorders and liver health, though challenges remain in delivery and efficacy. D'Agostino emphasizes the importance of formulation science, combining various molecules like ketones, electrolytes, and MCTs to optimize therapeutic outcomes, moving beyond single-molecule studies to complex interventions.
Mentioned in This Episode
●Supplements
●Products
●Companies
●Organizations
●Concepts
●People Referenced
Ketogenic Diet Protein & Fat Ratios
Data extracted from this episode
| Diet Type | Fat Percentage (Approx.) | Protein Percentage (Approx.) |
|---|---|---|
| Original Ketogenic Diet | 90% | 10% |
| Modified Clinical Ketogenic Diet | 60-70% | 20-30% |
| High Protein Ketogenic Diet (Weight Loss) | Moderate | High (e.g., 220g for 220lb active male) |
Ketone Supplement Effects on Insulin and Glucose
Data extracted from this episode
| Supplement Type | Rate of Ketone Elevation | Insulin Spike | Glucose Levels |
|---|---|---|---|
| Ketone Salts | Slower, less high | No | Lowered (no counter-regulatory dump) |
| Ketone Esters (large dose) | Rapid, high | Yes (proportional to rise) | Lowered (can lead to hypoglycemia) |
| 1,3-Butanediol (large dose) | Slower, high (via liver metabolism) | Yes | Lowered (hypoglycemic agent) |
Common Questions
Nutritional ketosis is a physiological state defined by blood beta-hydroxybutyrate levels above 0.5 millimoles per liter. It's achieved through carbohydrate-restricted diets, primarily high-fat (historically 90%, now 60-70% fat with higher protein), or through fasting. Insulin suppression mobilizes fatty acids, which the liver then converts into ketone bodies for brain fuel.
Topics
Mentioned in this video
A French physiologist whose seminal studies in the 1800s showed oxygen was a stimulant, leading to early understanding of 'caissons disease'.
Worked at the Mayo Clinic in the 1920s, helping establish the framework for early ketogenic diet therapies for epilepsy.
A stabilized NAD+ compound currently in clinical trials for potential therapeutic effects, possibly in combination with new ketone molecules.
Funding major studies on ketogenic diets for severe psychiatric disorders at multiple universities.
A clinic in The Villages, Florida that treats thousands of elderly patients with hyperbaric oxygen therapy, reporting remarkable increases in cognitive function and improved cardio-metabolic biomarkers.
An ACCME accredited medical education platform associated with the Metabolic Link podcast, providing educational content from experts on ketogenic metabolism.
Connected Peter Attia and Dom D'Agostino in 2011 and likely provided early information on 1,3-butanediol reports.
A ketone salt product containing a blend of sodium, calcium, magnesium, and potassium beta-hydroxybutyrate, designed to replenish electrolytes and provide exogenous ketones.
Communicated with Dom D'Agostino about the development of ketone salts, specifically balancing sodium with potassium.
A hexokinase inhibitor, used to target glucose in cancer cells as part of a metabolic therapy framework.
A drug used to target glutamine in cancer cells, binding it up and aiding in its excretion.
A type of drug (like Lonitamine) that inhibits hexokinase, an enzyme involved in glycolysis, used to create an energy crisis in cancer cells.
A colleague of Dom D'Agostino at the University of South Florida with a peripheral interest in eating disorders, initially skeptical of ketogenic diets for anorexia.
A class of drugs used to lower glucose levels, part of the strategy to target glucose in cancer metabolic therapy.
An HDAC inhibitor that binds glutamine, aiding in its excretion, used in cancer metabolic therapy.
Runs the hyperbaric oxygen facility at the University of South Florida, involved in a rigorous DoD-funded study on HBO for PTSD and TBI.
A large in-person event focusing on basic science, clinical science, and patient implementation strategies for metabolic therapies.
A receptor involved in signaling pathways through which L-beta-hydroxybutyrate exerts its effects.
Author of a guide on the ketogenic diet for cancer, recommended for those using the diet for cancer management.
Dom D'Agostino's colleague who advised him to look at acetoacetate when D-beta-hydroxybutyrate monoesters were not effective for seizures.
A compound with glutamine-inhibiting properties, considered for cancer metabolic therapy.
Dom D'Agostino's podcast, offering further information on metabolic health.
A compound with glutamine-inhibiting properties, considered for cancer metabolic therapy.
A figure in the Navy, part of the network at Duke University that did seminal studies on diving physiology and established dive tables.
A registered dietitian who spearheaded advanced ketogenic therapies, transitioning from conventional dietetics to ketogenic approaches for epilepsy and other conditions.
A clinic in Budapest, Hungary that uses a ketogenic form of the carnivore diet to treat various conditions, including type 1 diabetes, cancer, and neurological disorders, with convincing longitudinal blood work.
A figure in the Navy, part of the network that established dive tables to prevent oxygen toxicity, seizures, and nitrogen narcosis.
Author of books on the ketogenic diet, particularly for clinical conditions like epilepsy.
Developed a glycerol beta-hydroxybutyrate ester as part of ketone ester research.
Gave her husband, suffering from Alzheimer's, coconut oil and MCT oil after seeing promising patent information, leading to significant improvement and a long case report.
A company providing continuous glucose monitoring (CGM) and related health insights, for which Dom D'Agostino is an advisor.
The phenomenon where cancer cells preferentially use glycolysis for energy, even in the presence of oxygen, making them sensitive to glucose-targeting therapies.
Dom D'Agostino's mentor, whose lab retains historical pictures and insights into oxygen toxicity research.
A figure in the Navy, part of the network at Duke University that did seminal studies on diving physiology and established dive tables.
Conducted seminal studies on 40-day water-only fasts, observing the plateau of ketone levels.
A researcher from Case Western who pioneered work on ketone esters and performed seminal studies on 1,3-butanediol.
An expert in eating disorders at the University of San Francisco, running a promising study on anorexia and ketogenic diets.
Spearheading comprehensive metabolic approaches for Alzheimer's disease.
A company that sells Allulose, a sugar alternative, for which Dom D'Agostino advised.
A late mentor of Dom D'Agostino, who pioneered work on ketone esters and emphasized the energetic favorability of D-beta-hydroxybutyrate for ATP production.
Researcher who conducted work on D- and L-enantiomers of beta-hydroxybutyrate.
Published a study at UCLA showing improved survival metrics and quality of life in glioblastoma patients, presumably with metabolic interventions.
Working on MCTs and other ketogenic agents for Alzheimer's, and published research showing preserved brain ketone utilization with age.
Researcher whose work emphasizes the importance of protein, contrasting with lower RDA recommendations.
A coffee creamer product containing alpha-GPC, MCT, and L-theanine, used by Dom D'Agostino for sustained cognitive function.
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