Beyond being an alternative fuel source, the ketone body beta-hydroxybutyrate (BHB) functions as a signaling molecule. It acts as an HDAC inhibitor, which can activate genes that enhance the body's antioxidant and cellular defense mechanisms, a pathway of interest in cancer therapy.
A moderate level of blood ketones, around 1.2 to 2 millimolars, can have an anxiolytic (anxiety-reducing) effect. However, spiking ketone levels significantly higher, often through large doses of exogenous supplements, can paradoxically increase anxiety and lead to a subsequent crash.
Long-term, consistent use of ketone esters based on 1,3-butanediol, a very common formulation, may lead to liver toxicity. This risk exists even at doses that are not considered excessively high, such as those used by endurance athletes or in protocols for Alzheimer's.
Dr. Fred Hatfield, a famous powerlifter, reportedly achieved years of remission from metastatic prostate cancer by implementing a 'sardine fast.' This protocol involved consuming only one can of sardines per day for one week each month, similar to a fasting-mimicking diet.
The anxiolytic effect of ketosis has a clear neurochemical basis. Elevated ketones increase the levels of the enzyme GAD (glutamic acid decarboxylase), which converts the brain's primary excitatory neurotransmitter, glutamate, into its primary inhibitory (calming) neurotransmitter, GABA, creating a more stable neurological state.
Adding Medium-Chain Triglyceride (MCT) oil to exogenous ketone supplements (like BHB salts or esters) leads to a higher and more prolonged elevation of blood ketone levels than taking either substance alone. The MCT oil slows the absorption of the supplemental ketones, extending their effect.
Contrary to concerns from animal studies about endocrine disruption, human data and Dr. D'Agostino's self-experimentation with high doses (up to 30mg) show no suppression of key hormones like testosterone, LH, or FSH. This suggests it can be used safely for its neuroprotective and antioxidant benefits.
Dr. D'Agostino gives his aging, neutered dogs a Selective Androgen Receptor Modulator (SARM) to stimulate muscle protein synthesis and maintain vitality. This approach is analogous to Testosterone Replacement Therapy (TRT) in humans, aiming to counteract the loss of skeletal muscle mass associated with aging and hormonal changes.
Research published in Nature Medicine indicates that ketogenic and vegan diets impact the immune system differently. While a vegan diet tends to enhance the broad, non-specific innate immune system, a ketogenic diet was shown to augment the more specialized adaptive immune system (T-cells and B-cells).