Peter Attia MD375 - The ketogenic diet, ketosis, and hyperbaric oxygen: weight loss, cognition, cancer, and more
CHAPTERS
- 0:01 – 5:37
Dom's path from neuroscience to ketosis research
Peter and Dom recount how they met around 2011 and how Dom's neuroscience background led him to the ketogenic diet. A Navy-funded postdoc on oxygen toxicity seizures pushed him toward ketones, and a chance observation with glioblastoma cells in a hyperbaric chamber drew him into cancer research.
- •Peter and Dom connected around 2011 and went on to test early synthetic ketones together
- •Dom studied the brain stem networks that control respiration and how they respond to oxygen and CO2
- •An Office of Navy Research fellowship on CNS oxygen toxicity led him to the ketogenic diet because it works for seizure disorders when drugs fail
- •Glioblastoma cells placed in a hyperbaric chamber showed mitochondria lighting up and disappearing, which launched his cancer work
- 5:37 – 14:19
Oxygen toxicity in Navy diving and the ketone trials at Duke
Dom explains why the Navy cares about too much oxygen: closed-circuit rebreathers deliver nearly pure oxygen, which can trigger seizures at depth. He describes the mechanisms, the history of the problem, and current human trials at Duke testing whether ketosis delays seizure onset.
- •Rebreathers supply essentially 100% oxygen and scrub CO2, avoiding bubbles for stealth, but depth can cause a seizure within minutes
- •Oxygen is a stimulant that drives glutamate release, inhibits glutamic acid decarboxylase, and bursts reactive oxygen species
- •The stimulant effect of oxygen has been known for about 150 years, and Duke-linked researchers established the dive tables
- •Duke human studies push subjects to an EEG seizure and measure latency under dietary or supplemental ketosis
- •Funding comes through ONR, CDMRP and NAVSEA
- 14:19 – 18:58
Defining nutritional ketosis and its pleiotropic effects
Peter asks Dom to define nutritional ketosis, and Dom explains how fasting and carbohydrate restriction produce BHB and acetoacetate. He gives the 0.5 mmol/L threshold and describes the diet's broad physiological effects.
- •Fasting suppresses insulin and mobilizes fatty acids, which the liver turns into BHB and acetoacetate
- •Ketosis can come from fasting, diet, supplements or ketoacidosis
- •The original ketogenic diet was about 90% fat, while modified versions use 60–70% fat with more protein
- •Clinical ketosis is defined by BHB above 0.5 mmol/L
- •Dom calls the effects pleiotropic and says the diet changes fuel use, biochemistry and neuropharmacology
- 18:58 – 25:08
Ketogenic diets for epilepsy: history and response rates
The conversation covers the origin of ketogenic therapy at the Mayo Clinic in the 1920s, building on the observation that fasting controlled seizures. Dom gives response rates in drug-resistant epilepsy and describes slice experiments showing BHB silences seizure activity and protects neurons.
- •Fasting was known to control seizures, and the first ketogenic diet reports for epilepsy appeared in 1921
- •About two-thirds of children who failed drugs respond, with roughly 30–40% responding in adults
- •Some responders can stop the diet after a year or two and stay seizure-free
- •Sodium BHB reduced seizure-like activity in hippocampal slices and made them more metabolically resilient
- •The goal became studying both the diet and the most effective exogenous ketone
- 25:08 – 28:26
Dom's keto experience: tracking, protein and ketone meters
Peter asks about Dom's own use of the diet, and Dom recounts losing strength and learning the importance of protein and lipid monitoring. They then discuss common mistakes, such as not tracking, and the state of blood, breath, urine and continuous ketone monitoring.
- •Dom began checking ketones around 2009 and lost 10–15 pounds along with some bench press strength
- •Ketones spare muscle but do not replace adequate protein
- •The diet raised his LDL and ApoB, which he manages pharmacologically with a small dose of ezetimibe
- •Track macros, calories and ketones, since people can easily overeat fat
- •Blood is the gold standard, breath acetone can be informative, and continuous ketone monitors are emerging
- 28:26 – 36:30
Practical keto guidance: weight loss, protein and carbs
Dom frames clinical ketogenic therapy as distinct from 'internet keto' and recommends working with a dietitian for medical use. For weight loss, he advises high protein, moderate fat and high fiber. He explains satiety mechanisms and his own protein intake, and notes that electrolytes and gradual transition ease the start.
- •Clinical keto is a prescription metabolic therapy, and a gradual transition over four to six weeks improves adherence
- •Monitor lipids, ApoB, HbA1c and insulin, and watch for responses in ApoE4 carriers
- •For weight loss: high protein, moderate fat, high fiber, with 50–100 g of carbs if a third is fiber
- •Calorie tracking matters, and a modest 10–20% deficit does most of the work
- •Dom eats about 220 g of protein at 220 lb and says that protein needs rise with muscle, activity and age
- 36:30 – 48:20
Electrolytes, protein levels and reintroducing carbohydrates
Dom explains how ketone-bound electrolytes can ease the transition and offset sodium and fluid loss. He then discusses protein targets relative to the RDA and how he handles fruit, carb backloading and metabolic flexibility. He also warns about abrupt carb reintroduction after strict restriction.
- •Ketone electrolytes address the natriuretic and diuretic effects of starting a ketogenic diet
- •High protein means 20–30% of calories, and the RDA would not maintain Dom's muscle
- •Dom backloads carbs in the evening with berries, vegetables and a keto mousse
- •Tripling carbs while traveling in Greece left him six pounds lighter and feeling great
- •Reintroducing carbs after long restriction can cause GI, glucose and mood disruption, so titrate them back
- 48:20 – 53:10
The carnivore diet as an elimination and ketogenic approach
Peter raises the carnivore diet, and Dom explains how a fatty version can produce ketosis, especially in a calorie deficit. He considers it a potentially therapeutic elimination diet for autoimmune conditions and cites anecdotal and case-series evidence.
- •Fatty carnivore diets can produce ketosis, particularly under energy restriction
- •Dom believes carnivore can be therapeutic for autoimmune disorders as the ultimate elimination diet
- •Micronutrient concerns are limited, though magnesium may trend low
- •He cites anecdotal reports and Hungary's Paleomedicina case series as compelling
- •Practiced with fatty cuts, he sees carnivore as a form of ketogenic diet
- 53:10 – 1:07:07
1,3-butanediol and the origin of ketone esters
Peter and Dom review early exogenous ketones, starting with 1,3-butanediol, a precursor that the liver converts to BHB through an alcohol-dehydrogenase pathway. They compare it to ethanol metabolism, covering liver enzyme and narcotic concerns, and explain why monoesters and diesters were developed.
- •1,3-butanediol is a stable glycol that was studied in the 1960s and for NASA spaceflight food
- •It is metabolized like alcohol and can raise liver enzymes and cause intoxication at high doses
- •Alcoholic ketoacidosis serves as an analogy for runaway ketogenesis with an energy-depleted liver
- •Esters attach BHB or acetoacetate to 1,3-butanediol to deliver ketones quickly with less butanediol
- •The monoester was designed to avoid the drawbacks of drinking butanediol alone
- 1:07:07 – 1:18:07
Ketone salts: design, electrolytes and insulin response
Dom explains why he developed ketone salts with mixed cations and why chloride, not sodium itself, is the culprit in salt-sensitive hypertension. Salts help bridge the early diet transition and trigger less insulin release than esters at high doses.
- •BHB free acid is unstable and acidic, so salts bind it ionically to sodium, potassium, calcium and magnesium
- •Dom argues salt-sensitive hypertension is tied to sodium chloride rather than sodium BHB
- •Early keto causes an energy gap and electrolyte loss that salts help bridge
- •Rapid ketone rises above roughly 1.5–2 mM can trigger insulin release and later hypoglycemia, as seen with esters but not salts
- •One packet delivers 6–10 g of BHB and keeps ketones around 1–2 mM for about four hours
- 1:18:07 – 1:26:23
D- versus L-BHB enantiomers and racemic mixtures
They break down the mirror-image forms of BHB, which most meters measure only as D. Dom describes D-BHB as fast-burning fuel and L-BHB as a slower, timed-release signaling molecule. He explains why racemic mixtures may extend ketone elevation.
- •D-BHB is metabolized quickly while L-BHB is cleared three to four times slower
- •L-BHB may reach higher brain concentrations and retain signaling effects such as NLRP3 inflammasome suppression
- •Dom says a DL mix delivers D's energy and L's signaling
- •Finger-stick and continuous monitors measure only D-BHB
- •Pure D monoester did not control seizures in his early work, and he pointed to redox balance with acetoacetate
- 1:26:23 – 1:34:18
NAD, ketosis and emerging psychiatric applications
Dom links rapid D-BHB spikes to reductive stress and says NAD elevation is a central mechanism of ketosis. Peter challenges him on NAD precursor trials, and Dom says stabilized NAD forms are in development. They then turn to the growing clinical trial landscape, including anorexia and other psychiatric disorders.
- •Dom sees NAD as a hub in the benefits of ketogenesis and thinks formulation matters
- •Peter notes NR and NMN have shown little benefit, and Dom suggests delivery and stabilization are the problem
- •Dom points to 6,000 publications and 558 registered trials on ketogenic diets
- •About 40–50 trials target psychiatric disorders, many funded by the Baszucki group
- •Early data in anorexia look encouraging, and supplements may help adherence in psychiatric patients
- 1:34:18 – 1:46:36
Ketone supplementation for cognition, and the risks of high ketones
Peter asks whether supplements can replace the strict diet. Dom says supplements lower glucose but cannot replicate every benefit of carbohydrate restriction, and he warns that ketones above about 2 mM from esters can cause energy toxicity and acidosis. He sees roles for esters in acute medical settings and favors salts or MCT-blended formulas for most people.
- •Ketone supplements tend to lower glucose, possibly via reduced gluconeogenesis and improved insulin sensitivity
- •Animals pushed into ketoacidosis with esters, around 6–7 mM, became sluggish and sometimes died
- •Above 2–3 mM from supplements, insulin release, renal load and falling blood pH become concerns
- •Salts act as a natural buffer, and Dom favors salts for most people with a 1–2 mM sweet spot
- •Esters may suit acute care such as status epilepticus or TBI, and MCT can mitigate rate-of-rise problems
- 1:46:36 – 1:59:31
Ketogenic metabolic therapy for cancer and glioblastoma
Dom describes a 49-author framework for ketone metabolic therapy in glioblastoma, built on a glucose-ketone index of 1–4 plus drugs targeting glucose and glutamine. Peter presses on the lack of randomized trials and why they have not been done.
- •The framework aims to make metabolic therapy an adjuvant to standard of care in highly glycolytic cancers
- •The target is a glucose-ketone index of one to four, with glycolysis and glutamine inhibitors layered on top
- •Dom says the goal is to double or triple survival, not cure
- •No RCTs exist yet, though several trials are in progress and Dom cites a new UCLA study
- •Barriers include funding, heterogeneity, dietitian support and pharma competition for patients, and Peter suggests pancreatic cancer as a model
- 1:59:31 – 2:11:25
Ketogenic therapy for Alzheimer's disease and cognitive enhancement
Dom explains why he thinks glucose hypometabolism and inflammation make ketone therapy plausible in dementia, and says randomized trials remain ongoing. Patient selection and comprehensive formulas matter. He then shares his personal cognitive toolkit of alpha-GPC, MCT, caffeine and situational fasting.
- •Alzheimer's features glucose hypometabolism, while the brain's ability to use ketones appears preserved with age
- •Dom thinks inflammation drives disease and that ketogenic therapy reduces systemic inflammation
- •Acute ketone elevation improves cognition in deficit states, but long-term amyloid-PET trials are ongoing
- •Patient selection should favor those with marked glucose hypometabolism, and funders resist formula-based trials
- •Dom pairs alpha-GPC, MCT, caffeine and theanine and uses fasting situationally
- 2:11:25 – 2:20:29
Hyperbaric oxygen therapy for concussion, TBI and PTSD
Peter asks Dom's view on hyperbaric oxygen outside its FDA indications. They discuss protocols for concussion, the commitment of 40 sessions, soft chambers and mixed evidence. Dom describes a rigorous sham-controlled DoD-funded trial at USF in veterans.
- •Dom thinks hyperbaric oxygen can be remarkably effective for acute concussion in the first 48–72 hours, especially in kids
- •A standard protocol is around two atmospheres for 60–90 minutes with up to 40 sessions, though Dom says fewer might suffice
- •Soft chambers reach about 1.3 atmospheres
- •A DoD-funded trial found benefit in controls using hyperbaric air, which muddied the conclusions
- •A USF sham-controlled study of veterans with PTSD and brain injury should give preliminary data within a year
- 2:20:29 – 2:25:27
Peter's takeaways and Dom's resources
Peter reflects on slow progress in cancer and Alzheimer's trials versus the explosion in exogenous ketones, and says he'll try ketone salts. Dom names the product he uses, discloses his advisory roles and points listeners to his educational resources.
- •Peter notes insights on cancer and Alzheimer's have lagged due to a lack of clinical trials
- •Peter plans to try the salts, given no chloride concern and fewer GI issues than earlier salts
- •Dom recommends Keto Start by Audacious Nutrition and says his wife advises the company while he has no financial stake
- •Dom discloses advisory roles with Levels Health, MetPsy and RX Sugar
- •He points to the Metabolic Link Podcast and the Metabolic Health Initiative
