#845: How to Use Ketosis for Enhanced Mood, Cognition, and Long-Term Brain Protection — A Practical and Tactical Guide with Dr. Dominic D'Agostino (Plus: Deconstructing Tim’s Latest Keto Experiment)

The Tim Ferriss Show

Tim Ferriss: Bestselling Author, Human Guinea Pig

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4.6 • 17.4K Ratings

🗓️ 7 January 2026

⏱️ 142 minutes

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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] Who is Dominic D'Agostino?
[00:04:37] Ketosis benefits: Quieting the mind, GABA elevation, metabolic psychiatry.
[00:09:24] My Lyme disease story: Pseudo-dementia reversed in 3-4 days of ketosis.
[00:13:50] Spirochetes are glycolytic: Starve the bug, boost the immune response.
[00:19:20] Ketosis and cancer: Slowing glycolytic tumors, enhancing standard care.
[00:20:50] My 18-day keto experiment: Mood stabilization, Alzheimer’s prevention hopes.
[00:23:19] Metabolic memory: Carryover effects and Valter Longo’s fasting mimicking research.
[00:27:11] Intermittent fasting as keto on-ramp: My 2-8 p.m. eating window.
[00:29:15] Dom’s budget keto meal: Canned mackerel, MCT oil, apple cider vinegar.
[00:33:28] My ketone measurement paradox: Feeling sharp at 0.2 mM readings.
[00:36:56] The carburetor analogy: Ketone production vs. utilization explained.
[00:38:43] Breath ketones vs. blood ketones: Better indicator in caloric deficit.
[00:39:47] Gluconeogenesis fears: Fat, fiber, and salt to slow protein absorption.
[00:45:25] The bunless double cheeseburger question: 80 grams of protein in one sitting.
[00:49:03] Post-meal walking and GLUT4 activation: Timing your glucose disposal.
[00:51:02] CGM and ketone monitor limitations: When your devices gaslight you.
[00:58:05] Rabbit starvation and protein-veggie days: Why your body won’t bankroll its own ketosis.
[01:05:44] Alzheimer’s prevention: Biomarkers, B12, hsCRP, and metabolic health.
[01:09:40] My family history: Letrozole, metabolic dysfunction, and rapid cognitive decline.
[01:13:17] Minimum effective dose: 80% of benefits from low-carb Mediterranean.
[01:18:56] One week per month protocol: Aggressive calorie cut to ramp ketones.
[01:23:12] GKI sweet spot: Target 1-4, aim for 1-2 during intensive weeks.
[01:36:22] Exogenous ketones 101: Palatability, tolerability, pharmacokinetics, toxicity.
[01:39:21] 1,3-Butanediol warnings: Liver toxicity, NAD depletion, dependency risk.
[01:54:22] Intermittent fasting vs. ketogenic breakfast.
[01:59:09] My accidental intoxication story.
[02:03:23] Dr. Veech tribute: Student of Hans Krebs, ketone ester pioneer.
[02:05:08] Fiber on keto: Wild blueberries, broccoli, apples, walnuts.
[02:09:58] The tainted gummies incident: Dom’s forensic investigation underway.
[02:13:08] Thanks to Dr. Boz and Medifoodz.
[02:16:19] Parting thoughts.

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Transcript

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0:00.0	Hello, boys and girls, ladies and germs. This is Tim Ferriss. Welcome to another episode of the Tim Ferriss show.
0:05.2	This particular episode, I think, is probably my most practical, tactical discussion of ketosis.
0:13.6	What the benefits are, how to implement it, when the rubber hits the road, what do you do?
0:19.5	What do you do? What do you try to avoid?
0:21.0	What are some of the challenges? And this conversation with Dom Degasino, I'll describe him in a
0:25.9	second, took place about midway through a month-long experiment. I've done a lot of ketogenic dieting.
0:32.2	I've experimented with it since probably the late 90s. And my latest bout was one month wearing both a continuous glucose
0:41.9	monitor and a continuous ketone monitor. And we basically deconstructed it. And I got Dom's advice
0:48.4	on how to tweak it, how to fine-tune it. Now, why would you even want to consider ketosis? And we also
0:54.1	get into exogenous ketones.
0:56.3	So supplemental ketones. They've become quite the topic de jour, quite popular among certain
1:02.7	athletic populations and so on. But we talk about toxicity with some of these supplements and what
1:07.7	to look out for. We talk about ketone dependence and withdrawal.
1:12.0	We talk about before and after testing and lots of ways that you can be a bit smarter, a bit more
1:18.2	informed about approaching all of this. So the benefits, why would you even consider this?
1:22.8	Why have I myself spent so much time in ketosis, so to speak. Well, there are a few things. Immediately,
1:29.2	I will notice once I get to a certain concentration in my blood, and that's generally around,
1:34.6	let's just call it 0.7 millimolars measured with a finger prick, and then more as you get going.
1:40.7	I need less sleep. So instead of eight to nine hours, six hours, six and a half
1:46.1	hours, I wake up and I am wide awake. So that's another difference. I wake up and I am
1:50.6	wide awake alert ready to go. I don't need an hour of booting up and tons of caffeine to get
1:56.7	online. I am mentally sharper. My verbal acuity, my ability to think just has a faster turnover.
	...

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