Fisetin's senolytic activity is dose-dependent with a clear threshold effect. In mouse studies, doses below ~50 mg/kg show anti-inflammatory and neuroprotective effects without significant senescent cell clearance, while doses of 100 mg/kg (equivalent to ~8–20 mg/kg in humans after allometric scaling) consistently reduce SA-β-Gal positive cells by 25–50%.

Does taking more than 20 mg/kg provide additional senolytic benefit?

Evidence does not support significant additional benefit above the 20 mg/kg human protocol. GI tolerability decreases at higher doses without proportional senolytic improvement.

Can I use continuous low-dose fisetin as a substitute for burst dosing?

Low-dose continuous fisetin (100–200 mg/day) provides non-senolytic benefits but does not achieve senolytic plasma levels. Burst dosing is essential for senolytic action. Both approaches can be combined.