#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

What It Covers

Dr. Dominic D'Agostino explains ketogenic diet protocols, exogenous ketone supplementation strategies, and metabolic therapies for Alzheimer's prevention, cancer treatment, and mental health conditions, including specific dosing recommendations and potential liver toxicity concerns with certain ketone supplements.

Key Questions Answered

• •Ketone Supplementation Synergy: Combining exogenous beta-hydroxybutyrate with MCT oil increases ketone levels higher than either alone and sustains elevation by slowing absorption. Taking both together optimizes ketone availability for cognitive and metabolic benefits, particularly when targeting therapeutic ranges of 1.2-2.0 millimolar for anxiolytic effects.
• •Sardine Fasting Protocol: Dr. Fred Hatfield achieved cancer remission using one can of sardines daily for one week per month, combined with ketogenic diet. This approach provides omega-3 fatty acids to prevent muscle wasting while creating caloric restriction that activates autophagy and achieves glucose-ketone index of 1-2 for three to five days.
• •Liver Toxicity Warning: Chronic use of 1,3-butanediol-based ketone supplements above 100 milliliters daily shows potential liver toxicity in emerging research. Many commercial ketone products use this compound, making cycling and moderation essential. Alternative formulations using different ketone delivery mechanisms may be safer for long-term use.
• •Glucose-Ketone Index Targeting: Maintaining GKI between 1-5 provides metabolic benefits, with 1-2 being optimal for therapeutic applications. Normal population averages 25-50 GKI. Keto-Mojo device automatically calculates this ratio and costs approximately half the price of Precision Xtra strips while providing more accurate readings aligned with laboratory assays.
• •Metabolic Psychiatry Applications: Beta-hydroxybutyrate at 1-2 millimolar produces anxiolytic effects comparable to benzodiazepines by increasing GABA-to-glutamate ratios and activating glutamic acid decarboxylase enzyme. Ketone levels above 3 millimolar can paradoxically increase anxiety through metabolic acidosis, requiring careful dosing for mental health applications.