Tim FerrissAll Things Ketones, How to Boost Cognition, Sardine Fasting, Diet Rules, & More — Dr. Dom D’Agostino
CHAPTERS
- 0:00 – 0:52
Wine, blood viscosity, and platelet aggregation: Dom’s pushback on alcohol consensus
Dom opens by challenging broad claims about alcohol by pointing to studies he says are not specifically about wine. He describes his own observation that wine makes his blood “less viscous,” and connects that to decreased platelet aggregation and potentially less clotting risk.
- •Dom says wine-specific studies he found suggest decreased cancer risk
- •Dom reports observing reduced blood viscosity after wine, then finding it supported in literature
- •He says wine decreases platelet aggregation
- •He links decreased platelet aggregation to reduced potential for clotting and stroke
- 0:52 – 2:46
Why Tim is revisiting ketosis: family Alzheimer’s risk and APOE status
Tim explains he’s revisiting ketogenic strategies and exogenous ketones due to neurodegenerative disease in relatives, including Alzheimer’s. He shares his and his siblings’ APOE status and asks what evidence exists for ketogenic diets and/or exogenous ketones for prevention or symptom mitigation.
- •Tim describes neurodegenerative decline in family members, including Alzheimer’s
- •Tim shares his and siblings’ APOE status and concern about risk
- •He asks about data for ketogenic diets and exogenous ketones in Alzheimer’s across prevention and progression
- •Tim invites both evidence and informed speculation about future research directions
- 2:46 – 4:31
Mary and Steve Newport case observations: MCT/coconut oil and temporary symptom improvements
Dom recounts meeting Mary Newport and observing her husband Steve Newport’s response to raising ketones with coconut oil and MCT oil. He describes a pattern of temporary improvements—tremors stopping and increased animation—followed by decline hours later unless ketones were raised again.
- •Dom credits early adoption of the approach to people focused on brain energy metabolism in Alzheimer’s
- •He describes Steve Newport using coconut oil and MCT oil (later transitioning toward ketone ester use)
- •Dom says Steve’s tremors stopped and he became more animated after ketone intake
- •Dom reports the effect lasted about four hours, then waned until ketones were raised again
- 4:31 – 7:42
Mechanisms overview: glucose hypometabolism, inflammation, and possible infectious contributors
Dom broadens Alzheimer’s into a dementia spectrum and highlights glucose hypometabolism as a central feature that worsens with aging. He discusses neuronal glucose transport and pyruvate dehydrogenase changes, and argues neuroinflammation—potentially driven in part by infections—may contribute to metabolic dysregulation.
- •Dom describes Alzheimer’s as a “fuzzy” diagnosis and references multiple dementia-related contributors
- •He emphasizes age-related decline in neuronal glucose metabolism and mentions GLUT3 and pyruvate dehydrogenase complex
- •He identifies neuroinflammation and vascular factors as contributors to dysregulated metabolism
- •Dom says there is accumulating evidence that infections may contribute to Alzheimer’s and notes an NIH workshop that shifted his skepticism
- 7:42 – 8:26
Longevity framing: immune system as an additional “horseman” and the role of metabolic control
Dom proposes the immune system as an important additional driver of longevity risk beyond commonly discussed categories. He argues metabolic control and epigenetic regulation of immune function are increasingly central topics in longevity research.
- •Dom calls the immune system a “fifth horseman” for longevity and adds skeletal structure as another factor
- •He links longevity to metabolic control of immune system function and epigenetic regulation
- •He notes institutions and longevity clinics are paying increased attention to immune-metabolic control
- •Tim prompts a transition into practical measurement and tracking tools
- 8:26 – 9:43
Measuring ketones and GKI: device preferences, accuracy, and practical interpretation
Dom compares ketone and glucose meters, saying his lab historically used Abbott Precision Xtra but he often recommends Keto-Mojo for its GKI feature and strip costs. Tim describes discrepancies during an oral glucose tolerance test, and Dom explains meters can trend high and suggests interpreting readings alongside broader biomarkers and CGM data.
- •Dom says Abbott Precision Xtra was used historically in publications, but he recommends Keto-Mojo for GKI and strip price
- •Dom describes a trial comparing breath, urine, Precision Xtra, and Keto-Mojo, saying Keto-Mojo aligned better with lab assays
- •Tim reports Keto-Mojo glucose readings higher than phlebotomy values during OGTT
- •Dom says meters often read ~10% high and recommends looking at insulin, A1C, and HSCRP, and using CGM context
- 9:43 – 11:28
Fasting vs ketogenic diet vs exogenous ketones—and Dom’s “sardine fasting” approach
Tim asks what fasting does beyond keto, and what keto does beyond exogenous ketones, sharing his past fasting routines. Dom describes using fasting situationally and introduces “sardine fasting,” a fasting-mimicking pattern using limited sardines to create a deficit while maintaining nutrients.
- •Tim outlines his prior annual weeklong fast and quarterly three-day fasts and asks if Dom still fasts
- •Dom distinguishes multiple ways to create an energy deficit (caloric restriction, time-restricted feeding, cyclic keto, supplemented keto)
- •Dom introduces “sardine fasting” as his preferred fasting-mimicking strategy
- •He frames it as easier than water-only fasting while still creating caloric restriction
- 11:28 – 15:05
Sardine fasting origin story: Dr. Fred Hatfield, prostate cancer remission, and cadence
Dom tells a story about mentoring and supporting Dr. Frederick “Dr. Squat” Hatfield during advanced metastatic prostate cancer. He describes Hatfield’s low-carb/ketogenic eating plus periodic sardine-only intake, which Dom says coincided with rapid remission and long survival; Dom estimates the sardine fast was done about monthly.
- •Dom describes working with Dr. Frederick Hatfield (“Dr. Squat”) during advanced metastatic prostate cancer
- •He says Hatfield used a low-carb/ketogenic approach and a sardine-based fasting-mimicking pattern
- •Dom reports Hatfield went into rapid remission and later had “no evidence of disease,” living years beyond an initial short prognosis
- •Dom estimates Hatfield did a week of ~one can of sardines per day about once per month (sometimes every one to two months)
- 15:05 – 18:19
Tim’s hiatal hernia and cancer-risk concerns; Dom’s biomarkers emphasis (HSCRP, GKI)
Tim shares a personal medical discovery of a hiatal hernia and scarring from acid exposure, and asks whether fasting might help reduce risk. Dom explains he uses sardine fasting situationally and highlights HSCRP as a key cardiometabolic marker, saying it can be a better indicator of cardiovascular disease risk than LDL and is relevant across multiple disease areas.
- •Tim recounts endoscopy findings: hiatal hernia, throat scarring from acid, and concern about cancer risk
- •Dom explains he uses fasting episodically based on context like travel, workload, or feeling an inflammatory flare
- •Dom says his HSCRP became “non-detectable” after keto compared to higher levels on a higher-carb diet
- •Dom states HSCRP is a better indicator of cardiovascular disease risk than LDL and frames it as important across Alzheimer’s, cancer, and more
- 18:19 – 24:12
How sardine fasting is used in practice: cachexia concerns, omega-3s, autophagy targets, and OGTT/CGM lessons
Dom describes why he prefers sardine fasting for cancer patients versus water-only fasting, focusing on avoiding cachexia and leveraging omega-3s while maintaining a caloric deficit. He links multi-day low GKI ranges to a constellation of measurements associated with autophagy, while Tim emphasizes the value of OGTT and CGMs for catching metabolic dysfunction missed by fasting glucose alone.
- •Dom says he advises cancer patients to avoid water-only fasts to reduce risk of cancer cachexia
- •He highlights omega-3 fatty acids (from sardines) as “potent mitigators” of cachexia and notes sardines provide broad nutrition
- •Dom describes aiming for a GKI around 1–2 for multiple days as correlating with maximizing autophagy-related signals
- •Tim argues OGTT plus insulin (and/or CGM) can reveal dysfunction missed by fasting glucose snapshots
- 24:12 – 31:09
Sustaining ketosis long-term: baseline low-carb Mediterranean style, biomarkers, and cholesterol hyperabsorption (ezetimibe)
Tim asks about “keto memory” and how to balance strict keto, fasting, and exogenous ketones without burnout. Dom recommends a sustainable baseline low-carb Mediterranean-like approach with periodic ketosis, tracking biomarkers, and he discusses cholesterol hyperabsorption genetics and his use of ezetimibe to control ApoB/LDL while eating ketogenic.
- •Dom recommends a sustainable day-to-day protocol rather than constant strict keto
- •He suggests a low-carb Mediterranean-like baseline with periodic ketosis to optimize GKI
- •Dom lists biomarkers he monitors: insulin, HSCRP, A1C, triglycerides, ApoB, and Lp(a)
- •Dom says ~30% of people hyperabsorb cholesterol; he reports using ezetimibe (Zetia) monotherapy to cut ApoB and LDL significantly
- 31:09 – 32:53
Dom’s day-to-day diet details, fish choices, and his view on wine in blue zones
Dom explains the practical composition of his diet, including fish-forward meals, vegetables, and earlier dinner timing. He describes swapping or reducing certain foods (like heavy cream, egg yolks, and ground meat) and emphasizes small fish like chub mackerel; he also revisits moderate wine intake, noting his observations and travel impressions in Greek and Sardinian “blue zone” areas.
- •Dom describes his typical meals: eggs and chub mackerel for breakfast; fish/meat for lunch; large dinner with protein plus vegetables (often broccoli)
- •He explains dietary tweaks he made to address lipids, including reducing egg yolks and removing heavy cream
- •Dom describes choosing smaller fish (chub mackerel, sardines) and checking heavy-metal exposure due to high intake
- •He says in Greece and Sardinia he observed older adults commonly having alcohol after dinner and emphasizes factors like activity, sun, and social interaction
- 32:53 – 37:29
Dogs, ketones, SARMs, and rapamycin skepticism: how Dom thinks about interventions
Dom describes giving his dogs ketones for cognitive, anti-inflammatory, neuroprotective, and anticancer reasons, along with other supplements and (after an injury) a SARM. He explains why he has decided against rapamycin for now, citing immune suppression concerns and side effects he has seen in others.
- •Dom says he gives dogs ketones for brain, inflammation, neuroprotection, and anticancer considerations
- •He describes using a SARM (ostarine) for dogs after injury and explains SARMs as selective androgen receptor modulators
- •Dom discloses his wife created products under Audacious Nutrition and he does not sell products personally
- •He says he is not ready to use rapamycin due to immune suppression concerns and notes mouth sores reported by people he knows
- 37:29 – 46:07
Sleep disruption during fasting: electrolytes, GABA, diphenhydramine cautions, and melatonin rationale
Tim and Dom discuss sleep difficulty during fasting and caloric deficits, including sympathetic activation and elevated nighttime arousal. Dom describes using electrolyte/ketone mixtures, occasional GABA or low-dose diphenhydramine with cautions, and explains his long-term melatonin use primarily for neuroprotective effects rather than sedation, addressing concerns about endocrine disruption in humans.
- •Dom says caloric deficit can increase sympathetic activation, making sleep harder, and that sardine fasting reduces this versus zero-calorie fasting
- •He describes using an electrolyte/ketone mix (KetoStart) and eating sardines at night during sardine fasts
- •Dom mentions occasional low-dose diphenhydramine and warns against frequent use due to dementia concerns; he also cautions phenibut tolerance/addiction risk
- •Dom discusses melatonin: he paused it to check endogenous production, cites lack of evidence for endocrine suppression in humans, and says he uses it for neuroprotective effects
- 46:07 – 1:01:46
Immune modulation, shingles/herpes flare anecdotes, and innate vs adaptive shifts with diet states
Dom shares an anecdote about water-only fasting at first signs of shingles preventing progression for someone he spoke with. He discusses fasting/ketosis as influencing immune allocation and inflammatory tone, and references a study he describes in which vegan diets enhanced innate immune markers while ketogenic diets enhanced adaptive immune markers.
- •Dom describes an anecdote where water-only fasting at first tingling signs of shingles prevented it from surfacing
- •He frames fasting as reducing general inflammatory markers while shifting immune vigilance
- •Dom references research collaborations focused on ketone metabolic therapy and adaptive immune augmentation
- •He cites a study he says showed vegan diet enhancing innate immunity and a two-week ketogenic diet enhancing adaptive immunity
- 1:01:46 – 1:37:41
Research frontiers: cancer ketone metabolic therapy, metabolic psychiatry, and hyperbaric oxygen + ketosis synergy
Dom outlines key areas he’s most excited about: ketone metabolic therapy frameworks for cancers like glioblastoma and using ketones to augment immunotherapies, and the emerging field of metabolic psychiatry. He also describes major hyperbaric oxygen research efforts and explains why he thinks pairing hyperbaric oxygen with ketone metabolic therapy could enhance benefits and reduce seizure risk.
- •Dom highlights ketone metabolic therapy research for cancer, including a framework review for glioblastoma and work augmenting checkpoint inhibitors and CAR T-related immune effects
- •He discusses metabolic psychiatry growth, pointing to Chris Palmer’s work and institutions studying ketogenic therapy for multiple psychiatric disorders
- •He describes earlier animal findings: ketone supplementation producing anxiolytic-like behavioral effects and changes in GABA/glutamate-related markers
- •Dom details a large hyperbaric oxygen study for veterans with TBI/PTSS and argues ketone metabolic therapy could augment HBOT and lower oxygen-toxicity seizure risk
