In this AMA-style episode of the Optispan Podcast, Matt Kaeberlein reflects on six months of testosterone replacement therapy (TRT) while also fielding wide-ranging questions on longevity science, supplements, sleep, and emerging health trends. The discussion blends personal experience with evidence-based skepticism, making it accessible for a popular science audience interested in healthspan and aging.

Key Points:

This episode offers a candid look at how TRT can meaningfully change body composition and energy when clinically indicated. It balances personal results with scientific caution, especially around longevity interventions and health trends. The core message: prioritize evidence, avoid hype, and focus on sustainable foundations of healthspan.

• Testosterone Replacement Therapy (TRT)- Real, Measurable Changes: After six months on TRT, Matt reports noticeable increases in muscle mass, energy, and workout performance, attributing these primarily to direct hormonal effects rather than changes in training volume or intensity.
• Side Effects and Trade-offs of TRT: TRT increased appetite significantly and led to expected blood-marker changes, including higher hematocrit and lower HDL cholesterol, underscoring the need for regular monitoring and individualized dosing.
• Psychological Barriers to Hormone Therapy: Matt emphasizes that one of the biggest hurdles was accepting lifelong therapy and overcoming fear of injections—highlighting how stigma and mindset can delay effective medical treatment. 
• Rapamycin vs. Fasting for Longevity: Rapamycin has strong animal data supporting lifespan extension, while fasting appears to overlap mechanistically (via mTOR inhibition) but lacks comparable longevity evidence unless paired with calorie restriction. 
• Supplements- Useful but Secondary: Creatine (5 g/day) remains a “tier one” supplement for performance, while compounds like astaxanthin and glycine are promising but still secondary to foundational pillars such as sleep, exercise, nutrition, and hormones. 
• Health Hype vs. Pragmatism (Microplastics & HBOT): Matt cautions against fear-driven health narratives, arguing that issues like microplastics and hyperbaric oxygen therapy deserve measured concern and better data, not panic or expensive quick fixes.