Tim Ferriss is a self-experimenter and bestselling author, best known for The 4-Hour Workweek, which has been translated into 40+ languages. Newsweek calls him "the world's best human guinea pig," and The New York Times calls him "a cross between Jack Welch and a Buddhist monk." In this show, he deconstructs world-class performers from eclectic areas (investing, chess, pro sports, etc.), digging deep to find the tools, tactics, and tricks that listeners can use.
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Tim Ferriss is a self-experimenter and bestselling author, best known for The 4-Hour Workweek, which has been translated into 40+ languages. Newsweek calls him "the world's best human guinea pig," and The New York Times calls him "a cross between Jack Welch and a Buddhist monk." In this show, he deconstructs world-class performers from eclectic areas (investing, chess, pro sports, etc.), digging deep to find the tools, tactics, and tricks that listeners can use.
#825: Dr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More
The Tim Ferriss Show
1 hour 54 minutes 59 seconds
2 weeks ago
#825: Dr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More
Dr. Dominic D’Agostino (@DominicDAgosti2) is a tenured associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine and a Visiting Senior Research Scientist at the Institute for Human and Machine Cognition.
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Timestamps:
[00:00:00] Start.
[00:14:43] Why I'm interested in ketogenic strategies for neurodegenerative prevention.
[00:16:18] Mary and Steve Newport's ketone-linked temporary cognitive improvements.
[00:18:18] A mechanisms overview for Alzheimer's/dementia.
[00:21:25] The immune system as longevity's "fifth horseman" — and why metabolic control is key.
[00:22:04] How to measure ketones and GKI.
[00:23:00] Fasting vs. ketogenic diet.
[00:24:18] There's nothing fishy about sardine fasting.
[00:28:32] My hiatal hernia discovery and increased cancer risk concerns.
[00:30:04] HSCRP as a superior biomarker to LDL for cardiovascular risk.
[00:31:57] Glucose tolerance testing revelations and CGM importance.
[00:31:57] Upgrading the metabolic machinery through keto without getting bored.
[00:42:07] What do do if you, like Dom and me, are among the 30% who suffer from cholesterol hyperabsorption.
[00:43:42] Dom's day-to-day diet regimen.
[00:45:56] How Dom optimizes his aging dogs with ketones, SARMs, and supplements.
[00:51:30] Supplementing for sleep disruption while fasting.
[00:55:41] Why Dom doesn't have misgivings about melatonin.
[00:59:15] Shingles prevention through fasting protocols.
[01:00:15] Immune system modulation: Innate vs. adaptive, vegan vs. ketogenic.
[01:03:54] Dom at 50-something: Current meal timing and composition.
[01:05:57] Blue zone observations: Greek and Sardinian longevity habits.
[01:08:16] Ketogenic diet initiation tips: MCT, electrolytes, and fasted cardio.
[01:15:18] Ketone metabolic therapy for cancer.
[01:18:15] The metabolic psychiatry revolution.
[01:22:10] The soothing effects of hyperbaric oxygen and ketosis on seizure sufferers.
[01:28:27] Metformin vs. berberine.
[01:31:43] The low-dose neuroprotective potential of GLP-1 drugs.
[01:34:58] NAD research: MIB-626 and stabilized forms for mitochondrial health.
[01:39:48] Idebenone, CoQ10, and the Deanna protocol for ALS.
[01:42:05] Dom's supplement short list: CoQ10, creatine, ketones, vitamin D, melatonin.
[01:44:43] KetoNutrition.org, Metabolic Health Summit, Audacious Nutrition, veteran-focused research protocols, and other parting thoughts.
*
Show notes for this episode: https://tim.blog/2025/09/03/dr-dominic-dagostino-all-things-ketones/
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The Tim Ferriss Show
Tim Ferriss is a self-experimenter and bestselling author, best known for The 4-Hour Workweek, which has been translated into 40+ languages. Newsweek calls him "the world's best human guinea pig," and The New York Times calls him "a cross between Jack Welch and a Buddhist monk." In this show, he deconstructs world-class performers from eclectic areas (investing, chess, pro sports, etc.), digging deep to find the tools, tactics, and tricks that listeners can use.
