#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)

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Jan 7, 2026

Dr. Dominic D'Agostino, a metabolic researcher, shares insights on the benefits of ketosis for mood support and cognitive protection. He breaks down the science behind ketosis, discussing its physical effects and clinical applications, including cancer care. Tim shares his personal experience with ketosis following a tick-borne disease. They delve into the mechanics of metabolic adaptation, the importance of dietary fat, and practical keto strategies for longevity. Plus, Dominic gives tips on measuring effectiveness and the potential concerns with exogenous ketones.

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INSIGHT

Ketosis Sharpens Sleep And Alertness

Ketosis often reduces required sleep and increases morning alertness for Tim Ferriss.
He experiences sharper cognition and fewer afternoon energy dips while in ketosis.

INSIGHT

Ketosis Quietly Calms The Brain

Ketosis elevates GABA and lowers glutamate, producing a calming, seizure-suppressing effect.
That neuropharmacologic shift underlies ketosis' potential for metabolic psychiatry.

ADVICE

Lower Insulin With Ketosis

Use ketosis to lower insulin and shift metabolism toward fat oxidation when insulin resistance is present.
Expect diuretic and natriuretic effects, so monitor blood pressure and medications.

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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:

Gusto simple and easy payroll, HR, and benefits platform used by 400,000+ businesses: https://gusto.com/tim
Seed's DS-01® Daily Synbiotic broad spectrum 24-strain probiotic + prebiotic: https://Seed.com/Tim
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Coyote the card game, which I co-created with Exploding Kittens: https://coyotegame.com

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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