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Peter Attia MD#05 - Dom D’Agostino, Ph.D.: ketosis, n=1, exogenous ketones, HBOT, seizures, and cancer
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CHAPTERS
- 0:04 – 7:24
Episode Overview and Guest Introduction
Peter Attia previews the episode, warns that the first hour is highly technical, and says the discussion covers exogenous ketone types and a metabolic cancer playbook. He stresses that nothing said is medical advice, then welcomes Dom D'Agostino and recalls how they met.
- •The first hour is more technical than intended, and listeners are encouraged to skip ahead
- •Later segments cover ketone esters, salts and MCTs, and a metabolic oncology playbook
- •Dom is a research scientist, not a medical doctor, and the content is not medical advice
- •Attia and Dom met after a talk in Florida and bonded over self-experimentation
- 7:24 – 16:36
Hyperbaric Microscopy and Cancer Cells Under Oxygen Stress
Dom describes his PhD and postdoc work on how the brain and cells respond to extreme environments, including building a hyperbaric atomic force microscope. He explains how glioblastoma cells under hyperbaric oxygen produced excess superoxide and suffered membrane damage and mitochondrial breakdown.
- •Dom's work on diving physiology led to a hyperbaric atomic force and confocal microscope
- •U87 glioblastoma cells were packed with mitochondria and produced excess superoxide under hyperbaric oxygen
- •High oxygen pushed the cells past their antioxidant capacity, triggering lipid peroxidation and cell death
- •Reactive oxygen species act as growth signals for cancer but become lethal at high levels
- 16:36 – 20:18
Oxygen Toxicity Seizures and Hyperbaric Oxygen Therapy
Dom explains oxygen toxicity seizures in Navy rebreather divers, their glutamate/GABA mechanism, and how ketone esters raise resistance. The conversation moves to the approved clinical uses of hyperbaric oxygen therapy and the caution needed around traumatic brain injury.
- •Rebreather divers at 50 feet can get oxygen toxicity seizures within minutes
- •Seizures involve S-nitrosylation of glutamic acid decarboxylase and a shift in the glutamate-to-GABA ratio
- •Ketone esters increased resistance to oxygen toxicity, according to Dom
- •Hyperbaric oxygen has about 14–15 approved uses, such as wounds, decompression sickness and carbon monoxide poisoning
- •In Dom's rat studies, repeated hyperbaric doses worsened brain injury while a single dose reduced infarct size
- 20:18 – 48:09
From Ketones in the Dish to Cancer Metabolism and the Warburg Effect
Dom explains how adding beta-hydroxybutyrate to culture media slowed cancer cell growth, which led him toward the ketogenic diet and cancer research. Attia and Dom then discuss the Warburg effect, its history, and why it fell out of favor.
- •Cancer cells grew more slowly with 1–5 mM BHB, and healthy neurons did fine in low glucose with ketones present
- •Dom found the ketogenic diet is an effective anti-seizure strategy even when drugs fail
- •The Warburg effect is fermentation-based energy production even when oxygen is present
- •Interest in genetics overshadowed cancer metabolism, which has since returned through oncometabolite research
- 48:09 – 1:02:20
George Cahill's Starvation Experiments and Brain Fuel
Attia asks Dom to recount George Cahill's 40-day fasting studies. They cover how glucose stayed near 3 mM while ketones rose, the insulin-induced hypoglycemia experiment, and how the brain shifted to ketones for most of its energy.
- •Subjects fasted 40 days on water and minerals, with BHB reaching or exceeding glucose around day seven
- •Glucose was held near 3 mM through glycogen, amino acids and glycerol
- •Insulin pushed glucose to about 1 mM without symptoms because ketones stayed at 5–6 mM
- •After about 10 days, roughly 60% of brain energy came from BHB and 10% from acetoacetate
- •Dom says such studies could not pass animal ethics review today
- 1:02:20 – 1:16:50
How the Body Makes Ketones: Biochemistry and MCTs
Dom walks through starvation ketosis, the roles of BHB, acetoacetate and acetone, and how ketones feed into the Krebs cycle. He then describes his own early classical and modified ketogenic diets and how MCTs boost ketone levels.
- •The liver makes acetoacetate and then BHB, but cannot use ketones itself
- •Acetone is volatile and has some anticonvulsant effects at low levels
- •Ketones are a non-fermentable fuel, unlike glucose and glutamine
- •MCTs go straight to the liver, and Dom worked up to about 150 mL per day
- •Dom nearly made a mistake buying caprylic acid instead of caprylic triglyceride
- 1:16:50 – 1:25:42
Ketones, Seizures, Insulin and Glucose Lowering
The two discuss whether anti-seizure effects come from ketone fuel or glucose reduction, and whether exogenous ketones work without a diet. They explore why ketones lower glucose and insulin, and Dom shares his own insulin data.
- •MCT C10 may have anti-seizure properties independent of ketones
- •Exogenous ketones on a standard chow diet worked in several of Dom's rodent seizure models
- •Ketones lower glucose in a predictable, dose-related way, possibly via insulin release, insulin sensitivity or a hepatic redox shift
- •Dom's insulin fell below the reference range after weeks of heavy exogenous ketone intake
- 1:25:42 – 1:38:06
Measuring Ketones and NASA NEEMO Self-Experiments
Dom compares urine, blood and breath ketone measurement, including the strip colors and the devices he uses in the lab. He then recounts his 10-day NASA NEEMO saturation mission, where he saw ketones rise, glucose fall, testosterone drop and weight fall.
- •Urine strips detect acetoacetate, and roughly 80 mg/dL suggests meaningful ketosis
- •Blood meters such as Precision Xtra and Keto-Mojo read within about 10–15% of lab assays
- •Hydration status can distort urine readings
- •Long cold-water EVAs pushed Dom's glucose into the 30s–40s with high ketones
- •He lost weight and had a 25% drop in testosterone during the mission
- 1:38:06 – 1:59:53
Ketone Salts vs. Esters and the D/L Enantiomer Question
Dom explains the chemistry of ketone salts and esters, the history of exogenous ketones, and how Patrick Arnold's synthesis helped. They then discuss the racemic versus pure D forms, the role of acetoacetate in seizure protection, and Dom's ketone tolerance test.
- •Salts are ionic bonds with cations such as sodium, potassium, calcium and magnesium; esters are covalent
- •1,3-butanediol esters taste terrible, and Dom says potency is inversely proportional to taste
- •Most commercial salts are racemic D and L, and Dom has seen no evidence of harm
- •In his seizure models, BHB alone did not protect, but a roughly 1:1 BHB/acetoacetate ester did
- •Keto-adapted athletes clear a ketone load quickly, and Dom proposes a ketone tolerance test
- 1:59:53 – 2:11:35
A Metabolic Playbook for Cancer: The Press-Pulse Approach
Attia asks, with strong caveats, what a metabolic approach to a late-stage cancer such as glioblastoma would look like. Dom describes the press-pulse idea, with a continuous press through a glucose ketone index of 1–2 achieved by ketogenic diet, time-restricted eating, exogenous ketones and metformin, and discusses the case for a metabolic oncologist.
- •Dom suggests an FDG PET scan to document a glycolytic tumor
- •The press aims for a glucose ketone index of 1–2, compared with about 25–50 for the average person
- •Time-restricted ketogenic eating and exogenous ketones are tools for reaching that index
- •Low-dose metformin is part of the press protocol
- •Adrienne Scheck's mouse work found that ketosis made radiation far more effective in a glioblastoma model
- 2:11:35 – 2:27:21
The Pulse Protocol: Hyperbaric Oxygen, IV Vitamin C and Glycolytic Inhibitors
Dom details the pulse side of the approach, including hyperbaric oxygen schedules, IV vitamin C as a pro-oxidant, and glycolysis-targeting drugs. He also explains why he avoids antioxidants during cancer therapy and describes a gentler, comprehensive metabolic-based strategy.
- •Hyperbaric oxygen three times weekly at about 2.5 ATA for 60 minutes, started lower with GBM because of seizure risk
- •Oxygen dissolved in plasma reaches hypoxic tumor regions, reverses hypoxia and boosts oxidative stress in tumor cells
- •High-dose IV vitamin C acts as a pro-oxidant, and Dom says antioxidants should be avoided in cancer
- •2-deoxyglucose, dichloroacetate, 3-bromopyruvate and lonidamine are mentioned as glycolytic inhibitors, cycled two weeks on and two weeks off
- •Dom envisions a gradual combined approach and a brief low-dose insulin pulse to restrict fermentable fuel
- 2:27:21 – 2:32:01
Dom's Seven-Day Fast and Resilience in Ketosis
Dom describes his own seven-day fast and the low glucose and high ketone readings he reached with exogenous ketones. He explains how this motivated his research, and he recounts the deadlifts he performed at the end of the fast. Attia urges him to stop taking risks.
- •Dom's glucose got low enough that the meter did not read it, with ketones of about 4–5 mM
- •GLUT1 deficiency motivates him because affected people reportedly do not get cancer
- •He deadlifted 500 pounds for 10 and a one-rep 585 after the fast
- •He argues keto-adaptation could preserve physical and cognitive resilience in austere military conditions
- 2:32:01 – 2:43:20
Ketones as Epigenetic Signals, Kabuki Syndrome and Closing Resources
Dom says the biggest change in his thinking over five years is seeing BHB as an HDAC-inhibiting signaling molecule, with a Kabuki syndrome mouse model as an example. He then shares his website, the Metabolic Health Summit and social handles, and Attia closes with thanks and the standard disclaimer.
- •BHB acts as an epigenetic signal through histone deacetylase inhibition
- •In a Kabuki syndrome mouse model, nutritional ketosis rescued neuronal and behavioral features
- •Dom views mitochondrial health as the ultimate tumor suppressor
- •Resources include ketonutrition.org and the Metabolic Health Summit in Long Beach
- •Attia shares a friend's wife's long survival on a ketogenic diet and closes with a disclaimer
