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.
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As we age, the timing of calorie consumption becomes more critical than the quantity. One calorie consumed after 6 PM can have the metabolic impact of ten calories consumed before noon due to its effect on insulin production during sleep. This highlights the importance of front-loading caloric intake.
Research shows that while you might feel you look worse after a bad night's sleep, objective measurements of under-eye skin pigmentation do not change. The effect is purely subjective, impacting how you perceive your own appearance due to tiredness or stress.
A simple way to regulate your nervous system is to listen to birdsong. From an evolutionary perspective, birds only sing when there are no predators nearby. Hearing them subconsciously signals to our brains that we are safe, which in turn lowers cortisol levels, blood pressure, and breathing rate.
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.
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.
When addressing hormone imbalances, start at the base of the "hormone pyramid." Optimizing foundational hormones like cortisol (stress) and insulin (blood sugar) is essential, as they directly impact thyroid function and sex hormones like estrogen and testosterone.
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.
Unlike sedatives, DORA-class sleep aids (Dual Orexin Receptor Antagonists) work by inhibiting wakefulness, creating more natural sleep architecture. Research suggests this may improve the brain's ability to clear beta-amyloid and tau proteins linked to Alzheimer's disease, offering a potential preventative strategy.
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.
Ketones are a more efficient energy source than glucose, producing less metabolic “trash” (oxidative stress). Crucially, they can penetrate the blood-brain barrier and fuel brain cells even when they've become resistant to insulin, directly combating cognitive decline and brain fog.