Tadalafil (Low-Dose)

Tadalafil is a PDE5 inhibitor primarily approved for erectile dysfunction and benign prostatic hyperplasia, but its mechanism of action – systemic vasodilation via nitric oxide/cGMP signaling – has attracted interest in longevity medicine.

At low daily doses (2.5–5mg), tadalafil reduces systemic vascular resistance, lowers blood pressure, and improves endothelial function. Multiple RCTs demonstrate improvements in exercise capacity in heart failure patients. There is also evidence for improved insulin sensitivity, skeletal muscle perfusion, and modest testosterone support through improved testicular blood flow.

Emerging observational data suggest men who take PDE5 inhibitors regularly have lower rates of cardiovascular events and all-cause mortality, though causality is difficult to establish. The longevity community has taken interest in low-dose daily tadalafil as a cardiovascular-protective agent with a favorable safety profile relative to other pharmaceuticals.