What is Dr. Dom D'Agostino's preferred device for measuring ketones?

While the Abbott Precision Xtra has been used historically for publications, Dr. D'Agostino generally recommends the Keto Mojo device for personal use. It calculates the glucose-ketone index (GKI), has more affordable test strips, and provides readings more in line with biological assays.

What is sardine fasting, and how does it compare to water fasting?

Sardine fasting is a modified fasting-mimicking diet (similar to Walter Longo's approach but with animal protein). It involves consuming 1-2 cans of sardines daily for about a week, typically once a month or every two months. This approach aims to induce benefits like autophagy and alleviate cancer cachexia (muscle wasting) by providing adequate nutrition (especially omega-3s and protein) while creating a caloric deficit, contrasting with the complete caloric restriction of water-only fasting.

What are Dr. D'Agostino's daily dietary habits and meal timing?

Dr. D'Agostino typically eats three meals per day. A typical morning includes eggs and chub mackerel. Lunch is usually fish (or beef/chicken), and dinner is his largest meal, often a pound of beef, chicken, or fish with a large quantity of a fibrous vegetable like broccoli, and a cup of wild berries. He eats dinner earlier, around 5:00-5:30 p.m., followed by physical activity.

Does Dr. D'Agostino drink alcohol, and what are his thoughts on its health effects?

Dr. D'Agostino consumes one glass of low-alcohol, non-sugar dry farm wine every other night, always followed by physical activity like an evening walk. He notes that studies on wine specifically have shown benefits like decreasing cancer risk and platelet aggregation, making blood less viscous. He believes this distinguishes wine from generalized alcohol consumption, and references blue zone populations who also consume alcohol.

What supplements does Dr. D'Agostino recommend for mitochondrial health?

For mitochondrial health, Dr. D'Agostino considers ketones (both D and L beta-hydroxybutyrate) paramount. He is also excited about ongoing research with NAD+ supplements, specifically stabilized forms like MIB626 from Metro International Biotech, which aim to improve mitochondrial markers over long periods. Historically, he notes sirtuins, which rely on NAD+, were tied to resveratrol discussions.

What are the core supplements Dr. D'Agostino uses and recommends?

His staple supplement since 1993 is Creatine monohydrate, which he also gives to his dogs. Other recommendations include exogenous ketones (emerging as 'the next Creatine'), Vitamin D (with checked levels of 60-80 ng/mL), Melatonin (as a neuroprotective antioxidant), and Omega-3s (if not consuming enough fish, with Nordic Naturals being a trusted brand).

How does Dr. D'Agostino manage sleep issues during fasting, and what supplements help?

When experiencing hyper-alertness or dysphoria during fasting, Dr. D'Agostino uses a combination of GABA, Magnesium, and sometimes a small dose (25mg) of Diphenhydramine (Benadryl) to reduce sleep latency. He also takes 5-10mg of Melatonin nightly, primarily for neuroprotection rather than sleep, though it helps him feel calmer.

What role do infectious agents play in Alzheimer's and other psychiatric disorders?

Dr. D'Agostino believes neuroinflammation is a big driver of metabolic dysregulation in Alzheimer's, and accumulating evidence suggests that infections like Epstein-Barr, cytomegalovirus, and herpes simplex virus (HSV) can act as ideological agents, triggering immune responses that contribute to neuroinflammation. Similar links are being explored in metabolic psychiatry for various mental health conditions.

What are the latest developments in ketone metabolic therapy for cancer?

Dr. D'Agostino is excited about comprehensive research on ketone metabolic therapy for cancers like glioblastoma, breast cancer, and lung cancer at the Moffitt Cancer Center. The therapy aims to augment immune checkpoint inhibitors and CAR T-cell therapy, specifically by activating the adaptive immune system and expanding relevant T-cells to enhance cancer-specific immunity.

What is metabolic psychiatry, and who are the key figures in this field?

Metabolic psychiatry is a rapidly emerging field focusing on using metabolic interventions like ketogenic therapy and lifestyle changes to treat psychiatric disorders such as schizophrenia, bipolar disorder, major depression, anorexia nervosa, and anxiety. Key figures include Dr. Chris Palmer (Harvard), Sabahani Sethy (Stanford), Dr. Alli Houston (Oxford), and Dr. Georgia Ede (Harvard). Jan and David Bazooki (from Roblox) are significant philanthropists funding this research.

What is the status of hyperbaric oxygen therapy (HBOT) research for traumatic brain injury?

A large, innovative $28 million study at the University of South Florida is currently investigating hyperbaric oxygen therapy protocols for traumatic brain injury (TBI) in veterans, with and without PTSD. Early findings from other research suggest mild HBOT (40-60 sessions) can enhance cognitive function and reaction time. Dr. D'Agostino also suggests that ketone metabolic therapy could augment HBOT and decrease the risk of oxygen toxicity seizures.

All Things Ketones, How to Boost Cognition, Sardine Fasting, Diet Rules, & More — Dr. Dom D’Agostino

Tim Ferriss

Howto & Style4 min read98 min video

Sep 3, 2025|79,906 views|2,017|231

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Key Moments

TL;DR

Dr. Dom D’Agostino discusses ketones, fasting, diet rules, Alzheimer's, and metabolic health.

Key Insights

Ketogenic diets and exogenous ketones show promise for neurodegenerative diseases like Alzheimer's by providing an alternative energy source for the brain.

Fasting, including 'sardine fasting,' can induce autophagy and cellular cleanup, offering potential benefits for metabolic health and disease prevention, though it should be approached cautiously, especially for cancer patients.

Measuring ketones and glucose with devices like Keto Mojo provides valuable insights into metabolic flexibility, with the Glucose Ketone Index (GKI) being a key metric.

Metabolic psychiatry is an emerging field exploring the link between diet, metabolism, and mental health conditions like depression, bipolar disorder, and anxiety, with ketogenic therapies showing promise.

Personalized nutrition and metabolic interventions, including dietary approaches, fasting, and potentially supplements or medications, are crucial for optimizing health, especially concerning genetic predispositions like APOE4.

Proper supplementation, including electrolytes, MCTs, and potentially NAD+ precursors, can support ketogenic adaptation and overall health, with individualized needs being paramount.

KETOGENIC THERAPIES AND NEURODEGENERATIVE DISEASES

Dr. Dom D’Agostino highlights the emerging research into ketogenic diets and exogenous ketones for conditions like Alzheimer's disease. The brain's reduced ability to metabolize glucose, often termed 'Type 3 Diabetes,' makes an alternative energy source like ketones crucial. Case studies and ongoing research suggest that ketones can serve this role, potentially mitigating symptoms and slowing disease progression. This area is rapidly evolving, with particular interest in the metabolic underpinnings of neuroinflammation and potential infectious triggers for Alzheimer's.

THE ROLE AND METHODS OF FASTING

Fasting, whether water-only or modified like 'sardine fasting,' is discussed as a potent tool for inducing autophagy and cellular repair. Sardine fasting, involving a specific caloric intake from sardines, is presented as a way to achieve caloric restriction while providing essential nutrients, particularly omega-3 fatty acids, which can help prevent cancer cachexia. Fasting is also recognized for its ability to modulate the immune system and reduce inflammation, making it a valuable, albeit situational, practice for metabolic health.

METABOLIC MONITORING AND INSIGHTS

Accurate monitoring of metabolic markers is essential for understanding one's health status. Dr. D’Agostino discusses the utility of devices like the Keto Mojo for measuring ketones and glucose, emphasizing the importance of the Glucose Ketone Index (GKI). While home devices may have slight variations compared to lab tests, they provide crucial real-time data for optimizing ketogenic diets and fasting protocols. He also stresses the significance of broader metabolic health markers beyond fasting glucose, such as insulin levels, CRP, and APOB.

METABOLIC PSYCHIATRY AND MENTAL WELL-BEING

The conversation delves into metabolic psychiatry, an emerging field that connects diet and metabolism to mental health. Ketogenic therapies are being explored for conditions like depression, bipolar disorder, and anxiety, as they can alter brain energy metabolism and neurotransmitter balance (e.g., increasing GABA relative to glutamate). Research suggests that neuroinflammation, potentially triggered by infections or other factors, plays a role in psychiatric disorders, and metabolic interventions may help mitigate this.

DIETARY STRATEGIES AND PERSONALIZED APPROACHES

Dr. D’Agostino advocates for personalized dietary strategies, often favoring a low-carb, Mediterranean-style approach as a baseline. He emphasizes the importance of adequate fiber intake, even within a ketogenic framework, and suggests strategic fluctuations in ketosis for optimization. For individuals with specific genetic predispositions like APOE4, or those concerned about lipid markers, tailored diets focusing on whole foods, healthy fats, and sufficient protein are recommended.

SUPPLEMENTATION AND MITOCHONDRIAL HEALTH

Key supplements discussed for supporting ketogenic adaptation and overall health include electrolytes, MCT oil, and exogenous ketones. The role of NAD+ precursors for mitochondrial health and DNA repair is highlighted, alongside creatine for its potential neuroprotective benefits. While research is ongoing, compounds like CoQ10 and omega-3 fatty acids also play significant roles in cardiovascular and cognitive function, with personalized monitoring being crucial for optimal intake.

ADVANCING RESEARCH IN CANCER AND BRAIN INJURY

Current research frontiers include ketone metabolic therapy for various cancers, particularly glioblastoma, aiming to enhance the efficacy of immunotherapy. Another area of significant excitement is hyperbaric oxygen therapy for traumatic brain injury, with large-scale studies underway to elucidate its true potential. Dr. D’Agostino also touches upon the potential synergistic effects of combining ketogenic therapies with hyperbaric oxygen to improve outcomes and manage risks.

UNDERSTANDING ALCOHOL AND LONGEVITY

The nuanced role of alcohol, specifically wine, is briefly discussed in contrast to the general consensus. Some studies suggest wine may decrease blood viscosity and platelet aggregation, potentially impacting clotting risk. This is linked to observations in 'Blue Zones' where moderate alcohol consumption, often wine or ouzo, is a common practice among centenarians, hinting at multi-factorial lifestyle contributors to longevity.

Mentioned in This Episode

●Supplements

●Products

●Software & Apps

●Tools

●Companies

●Organizations

●Concepts

●People Referenced

Ketogenic & Fasting Protocols for Health Optimization

Practical takeaways from this episode

Do This

For Alzheimer's prevention, consider a low-carb Mediterranean-like diet and situational ketosis or exogenous ketones.

Monitor metabolic biomarkers regularly: CBC, insulin, HS-CRP, Hemoglobin A1C, triglycerides, ApoB, LP(a).

If LDL spikes on a ketogenic diet, implement a low-carb pescatarian diet (under 100g carbs/day, 25% fiber).

If you're a cholesterol hyperabsorber, medication like Ezetimibe (Zetia) can effectively lower LDL and ApoB.

For cancer patients, use sardine fasting to prevent cachexia and benefit from omega-3s, avoiding water-only fasts.

To ease into a ketogenic diet, perform fasted low-intensity cardio, stay hydrated, take electrolytes (e.g., KetoStart), and use MCT oil/powder.

Consider 5-10mg of Melatonin as a neuroprotective antioxidant at night; it's generally safe for humans.

For sleep during fasting, try GABA, Magnesium, and occasionally 25mg of Diphenhydramine (avoid daily use).

Supplement with Creatine monohydrate (5-10g/day, up to 20g for advanced Alzheimer's), Vitamin D (60-80 ng/mL levels), and Omega-3s (if fish intake is low).

For mitochondrial health, ketones (D and L beta-hydroxybutyrate) are paramount, and NAD+ precursors are promising.

Avoid This

Avoid daily use of over-the-counter sleep aids like Diphenhydramine (Benadryl) at 50mg, as it may contribute to dementia.

Do not guzzle ketone esters as they can spike ketones too high, inhibiting endogenous production and potentially causing metabolic acidosis at levels above 3 mmol/L.

Do not solely rely on fasting glucose tests; request an Oral Glucose Tolerance Test (OGTT) with insulin measurements for a comprehensive metabolic picture.

Avoid consuming medicinal mushrooms like Lion's Mane, Reishi, or Cordyceps daily; cycle on and off for best effect.

Do not take creatine, caffeine, and MCT oil simultaneously when starting out unless you know how your body reacts.

Do not rely solely on wine studies to justify chronic alcohol consumption, as general consensus points to its detrimental effects.

Avoid high doses of Alpha-GPC if you experience headaches.

Be cautious with Phenibut; small, infrequent doses are tolerable, but high or frequent use can lead to addiction and severe withdrawal.

Common Questions

Exogenous ketones and the ketogenic diet are emerging areas of research for Alzheimer's prevention and mitigation. Dr. D'Agostino recounts observing symptomatic improvement in an Alzheimer's patient with MCT and coconut oil, highlighting metabolic dysfunction and neuroinflammation as central to the disease. Ketones provide an alternative brain energy source and can suppress inflammation.

Topics

Sardine Fasting SGLT2 Inhibitors

Mentioned in this video

softwareGB Health Watch

A genetic test that identified Dr. D'Agostino's NPC1L1 receptor mutation causing hyperabsorption of cholesterol.

personJan and David Bazooki

Billionaire philanthropists known for Roblox, funding metabolic psychiatry research at Stanford, Harvard, and Oxford.

organizationDepartment of Defense (DoD)

Funded early work on hyperbaric oxygen therapy, though initial research was 'muddy waters'.

personDr. Peter Attia

Mentioned for his 'four horsemen' of disease, with Dr. Dom D'Agostino adding immune system and skeletal structure as additional 'horsemen'.

supplementAudacious Nutrition KetoStart

A brand of ketones used by Dr. D'Agostino, developed from research on cancer, neurodegeneration, and seizures.

supplementBeta-hydroxybutyrate monoester

A ketone ester used in a case report for Alzheimer's disease by Dr. Mary Newport.

supplementCordyceps mushroom

A medicinal mushroom included in a supplement given to Dr. D'Agostino's dogs.

personDeanna Toadon

An ALS patient who has been stabilized for over a decade using the Deanna Protocol.

personDr. Alli Houston

At Oxford, collaborating on the Metpsy.com app.

supplementDihydroberberine

A more potent version of berberine, which caused Dr. D'Agostino a headache after about a week of use.

personDr. Angela Poff

Colleague who co-runs the Metabolic Health Initiative.

toolHyperbaric Oxygen Therapy (HBOT)

Research on HBOT protocols for traumatic brain injury (TBI) is promising, showing enhanced cognitive function. A large, innovative study is ongoing at the University of South Florida.

personDr. Iain Campbell

From Edinburgh University, published elegant reviews on hyperglycolytic effects in bipolar disorder and related research.

personSteve Newport

Husband of Dr. Mary Newport, subject of an early case report on ketones for Alzheimer's, observed to have symptomatic improvement with MCT and coconut oil.

personDr. Richard Vee

From the NIH, also involved in early Alzheimer's case reports.

toolAbbott Precision Xtra

A device historically used to measure ketones for publications, but less recommended for personal use due to strip cost and availability.

conceptHiatal hernia

A condition where the stomach pushes through the diaphragm, leading to scarring from acid and increased risk of esophageal cancer.

companyNeutriost

A brand from which Dr. D'Agostino bought straight MCT powder and C8 powder.

supplementNAD+ supplements (NR, NMN)

Supplements like Nicotinamide Riboside and Nicotinamide Mononucleotide are being researched for mitochondrial health, but liver and muscles tend to be greedy, reducing delivery to the brain.

supplementIdebenone

A drug-stabilized form of CoQ10, part of the Deanna Protocol for ALS, which became a standard of care for Friedreich's ataxia.

toolOmega Quant test

A test to measure DHA and EPA levels, used to confirm omega-3 status.

productChub mackerel

A small fish, low in heavy metals, consumed regularly by Dr. D'Agostino as a source of omega-3s and protein.

productDry Farm Wines

Low-alcohol, non-sugar wines consumed by Dr. D'Agostino every other night, noting their study-backed potential to decrease cancer risk and platelet aggregation.

productAudacious Nutrition Keto Spike Coffee

A coffee blend containing BHB electrolytes, used by Dr. D'Agostino in the afternoon as a non-caffeinated beverage.

companyMetro International Biotech (MIB626)

A company with phase 2 and 3 trials for Alzheimer's using a stabilized form of NAD+ (MIB626) and other NAD+ molecules.

conceptDeanna Protocol

A protocol developed for Deanna Toadon, an ALS patient, that included Idebenone and has been credited with stabilizing her advanced ALS for over a decade.

supplementLion's Mane mushroom

A medicinal mushroom included in a supplement given to Dr. D'Agostino's dogs.

conceptAPOE34

A genotype indicating a higher probability of developing Alzheimer's disease.

conceptType 3 Diabetes

A term coined in 2005-2006 for Alzheimer's disease, highlighting its metabolic dysfunction.

conceptEpstein-Barr virus

Mentioned as a potential infectious agent contributing to Alzheimer's disease, increasing MS risk by 4-5 times.

conceptCytomegalovirus

Mentioned as an infectious agent that can contribute to Alzheimer's disease.

conceptHerpes Simplex Virus (HSV)

Mentioned as an infectious agent that can contribute to Alzheimer's disease, Steve Newport having had bouts of HSV around his eyes.

personDr. Thomas N. Seyfried

A good friend and colleague, known for his research on metabolic therapy for cancer and adamant about maintaining a GKI of 1-2.

conceptSardine fasting

A modified fasting-mimicking diet where one or two cans of sardines are consumed daily for a week, used by Dr. Hatfield for cancer remission and by Dr. D'Agostino situationally to avoid muscle loss.

conceptHS-CRP (High-sensitivity C-reactive protein)

A cardiovascular biomarker and marker of inflammation, considered a better indicator of cardiovascular disease than LDL cholesterol.

toolOral Glucose Tolerance Test (OGTT)

A diagnostic test for metabolic dysfunction, recommended by the host for its accuracy over fasting glucose tests.

productStella device

A new over-the-counter CGM mentioned in passing.

personDr. Spencer Nadolsky

A doctor who proactively suggested Dr. D'Agostino take the GB Health Watch test.

supplementAudacious K9 supplement

A supplement created by Dr. D'Agostino's wife, containing spirulina, ketones, and other ingredients, given to their dogs for brain boosting, anti-inflammatory, neuroprotective, and anti-cancer effects.

supplementSpirulina

An ingredient in Audacious K9 supplement, given to dogs.

supplementSARM (Selective Androgen Receptor Modulator) - Ostine

An anabolic compound that stimulates skeletal muscle protein synthesis and bone metabolism, given to Dr. D'Agostino's fixed male dogs after injury to improve lean mass and strength.

supplementReishi mushroom

A medicinal mushroom included in a supplement given to Dr. D'Agostino's dogs.

conceptMTHFR

A genetic mutation related to folate metabolism, mentioned by Charles Poliquin in relation to French women's health.

supplementQuest MCT powder

A commercially available MCT powder, recommended by Dr. D'Agostino for ease of access.

personMatt Bazooki

Son of Jan and David Bazooki, who achieved durable remission from a psychiatric disorder with metabolic therapy.

softwareMetpsy.com

An emerging comprehensive app developed in collaboration with Dr. Alli Houston and Dr. Georgia Ede, incorporating ketogenic therapy, lifestyle, and coaching for mental health.

personDr. Georgia Ede

A Harvard psychiatrist, collaborating on the Metpsy.com app.

conceptGlutamic acid decarboxylase (GAD)

An enzyme that converts excitatory glutamate to brain-stabilizing GABA; its protein levels were higher in studies with exogenous ketones.

personNavdeep Chandel

From Northwestern, his view was that metabolically healthy people doing exercise and a good diet might not benefit much from Metformin.

organizationMetabolic Mind

Part of the Bazookis' Metabolic Psychiatry group, focuses on education related to metabolic health for mental disorders.

supplementCoQ10 (Ubiquinone/Ubiquinol)

A commonly recommended supplement for cardiovascular health, especially for those on statins or Metformin, though high doses in animal models showed kidney toxicity.

companyNordic Naturals

A recommended legitimate brand for omega-3 supplements for those who don't consume enough fish.

organizationKeto Nutrition

Dr. D'Agostino's informational website, ketonutrition.org.

personVictoria Field

Colleague who co-runs the Metabolic Health Initiative.

organizationUniversity of South Florida (USF)

Dr. D'Agostino co-teaches at USF and mentions a large hyperbaric oxygen therapy study taking place there.

conceptTraumatic Brain Injury (TBI)

A condition being studied in relation to hyperbaric oxygen therapy, with promising results for cognitive function.

drugproton pump inhibitors (PPIs)

productcoconut oil