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.
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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. 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.
While short-term keto adaptation (first month) may show no power gains, long-term adaptation (6-18 months) trains muscles to efficiently use fat as fuel. This results in significant power increases, with studies on soldiers showing up to a 50% improvement over their non-keto counterparts.
Focusing on building muscle is crucial for long-term health, particularly for women entering perimenopause. Muscle helps regulate blood sugar, reduces inflammation, and protects against osteoporosis, dementia, and heart disease, making it a vital health indicator.
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.
Instead of chasing weight loss, focus on foundational health markers like inflammation, blood sugar balance, stress levels, and nutrient deficiencies. When these systems are optimized, sustainable weight loss and body recomposition often occur as a natural side effect.
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.
The Orphan Drug Act successfully incentivized R&D for rare diseases. A similar policy framework is needed for common, age-related diseases. Despite their massive potential markets, these indications suffer from extremely high failure rates and costs. A new incentive structure could de-risk development and align commercial goals with the enormous societal need for longevity.
Modern ethical boards make certain human studies, like extended fasting, nearly impossible to conduct. This creates an opportunity to revisit older, pre-regulatory research from places like the Soviet Union. While the proposed mechanisms may be outdated, the raw data could unlock valuable modern therapeutic approaches.
A major pitfall of intermittent fasting is the loss of lean muscle tissue. To counteract this, it must be combined with dedicated resistance training. This combination allows for the metabolic benefits of fasting while signaling the body to retain and even build muscle, which can be tracked through strength gains.