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The Tim Ferriss Show

#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

Tim Ferriss: Bestselling Author, Human Guinea Pig

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4.617.4K Ratings

🗓️ 3 September 2025

⏱️ 115 minutes

🧾️ Download transcript

Summary

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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Transcript

Click on a timestamp to play from that location

0:00.0

Hello, boys and girls, ladies and germs. This is Tim Ferriss. Welcome to another episode, where it is

0:04.8

yet again my pleasure after more than a decade to deconstruct world-class performers from all

0:09.7

different disciplines to tease out the news you can use, the tactics and specifics that you can

0:15.1

apply to your own life. My guest today is a very popular and repeat guest on this show, Dr. Dominic D'Agostino.

0:23.9

He is a tenured associate professor in the Department of Molecular Pharmacology and Physiology

0:28.5

at the University of South Florida, Morsani College of Medicine, and a visiting senior research

0:33.1

scientist at the Institute for Human and Machine Cognition. He's also one hell of an athlete. And if you were to

0:40.3

ask me to name one person to ask any question related to ketosis, exogenous ketones, in other words,

0:48.2

supplemental ketones, anything at all related to the ketogenic diet, metabolic psychiatry,

0:53.8

if I had to choose someone who

0:55.1

was a decathlet of the highest order across all of those, it would be Dominic or Dom. He teaches

1:01.5

medical neuroscience, physiology, nutrition, and neuropharmacology, and his research focuses on

1:06.4

the development and testing of nutritional strategies. We'll talk about that. And metabolic-based

1:11.1

therapies for neurological disorders, whether it's depression or chronic inflammation,

1:16.7

cancer and human performance optimization. He has served as a research investigator and crew

1:21.6

member on NASA's Extreme Environment Mission Operations, and his research has been supported by

1:26.4

the Office of Naval Research, the Department of Defense, the National Institutes of Health, and his research has been supported by the Office of Naval Research,

1:28.4

the Department of Defense, the National Institutes of Health and Nonprofit Foundations, among

1:33.2

others. We get into a lot in this episode. We get very much into the weeds, so I thought

1:38.2

I would do something that I rarely do and just share a few of my takeaways. And these are just

1:43.7

a small sampling, but I wanted to mention a few

1:45.8

things. For instance, I've been taking various types of supplemental ketones, and they come in

...

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