#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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ADVICE

Combine Low-Carb With Periodic Ketosis

You can gain ~80% of ketosis benefits with a low-carb Mediterranean diet plus periodic deeper ketosis weeks.
Avoid chronically very high ketone levels; aim for therapeutic ranges rather than extremes.

ADVICE

Aim For A Practical GKI Range

Target a glucose-ketone index (GKI) of ~1–4 during therapeutic ketosis weeks; aim for 1–2 for stronger effects.
Use finger-prick glucose and BHB tests and consider exogenous support and MCTs to reach targets safely.

INSIGHT

Ketones Improve Brain Energy And Blood Flow

BHB at ~1 mM supplies ~10% of brain energy and also improves cerebral blood flow and vascular function.
L-isoforms of BHB may enhance vascular effects and improve brain perfusion.

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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:

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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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