#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

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Sep 3, 2025

Dr. Dominic D’Agostino, an associate professor with a focus on nutritional strategies for neurological health, dives into fascinating topics like the benefits of ketones for cognitive function and Alzheimer's prevention. He shares insights on sardine fasting's surprising health benefits and the connection between immune system health and longevity. Additionally, they explore the significance of metabolic measurements and dietary strategies that support brain health, revealing practical tips for enhancing cognitive performance and managing overall wellness.

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Measure Ketones And GKI At Home

Use a reliable meter like Keto-Mojo for home ketone and glucose monitoring because it calculates GKI and aligns well with lab assays.
Track glucose, ketones and compute GKI to target therapeutic ranges (e.g., GKI 1–5, optimal ~1–2).

Sardine Fasting As A Fast-Mimic

Try 'sardine fasting': eat one can of sardines per day for a week periodically to create a fasting-mimicking caloric deficit while preserving nutrition.
The protocol supplies omega-3s and protein to mitigate cachexia while suppressing insulin and mTOR.

Fred Hatfield's Remission Story

Fred Hatfield, with metastatic prostate cancer, used low-carb/keto plus monthly sardine-fasting and went into long remission, living years beyond prognosis.
He reported feeling better during the cycles and repeated them monthly or bimonthly.

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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.

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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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