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#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

September 3, 2025
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The Tim Ferriss Show

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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. This episode is brought to you by: Helix Sleep premium mattresses: https://HelixSleep.com/Tim (27% off all mattress orders) Momentous high-quality creatine: https://livemomentous.com/tim (code TIM for up to 35% off) AG1 all-in-one nutritional supplement: https://DrinkAG1.com/Tim (1-year supply of Vitamin D plus 5 free AG1 travel packs) 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/ For show notes and past guests on The Tim Ferriss Show, please visit tim.blog/podcast. For deals from sponsors of The Tim Ferriss Show, please visit tim.blog/podcast-sponsors Sign up for Tim’s email newsletter (5-Bullet Friday) at tim.blog/friday. For transcripts of episodes, go to tim.blog/transcripts. Discover Tim’s books: tim.blog/books. Follow Tim: Twitter: twitter.com/tferriss  Instagram: instagram.com/timferriss YouTube: youtube.com/timferriss Facebook: facebook.com/timferriss  LinkedIn: linkedin.com/in/timferriss See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.