Fisetin Dosage Calculator

What is Fisetin?

Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a polyphenolic flavonoid found in highest concentrations in strawberries (160 mcg/g), followed by apples, persimmons, and cucumbers. A 2018 study by Yousefzadeh et al. (EBioMedicine, PMID 30279143) from the Mayo Clinic established fisetin as arguably the most potent natural senolytic compound identified: it reduced senescent cell burden in multiple tissues in both young and aged mice, and — critically — extended median and maximum lifespan in aged (24-month-old) mice by approximately 10% when treatment began in late life. This demonstrates meaningful healthspan/lifespan extension even when started in old age, a therapeutically critical finding. Senolytic activity is fisetin's primary anti-aging mechanism. Like quercetin, fisetin inhibits pro-survival pathways (PI3K/Akt/mTOR, Bcl-2/Bcl-xL) that senescent cells upregulate as anti-apoptotic defences, while normal cells — which rely on these pathways less exclusively — are relatively spared. The Yousefzadeh study demonstrated that fisetin was more effective than quercetin, dasatinib, navitoclax, and 10 other candidate senolytics in direct comparison screening. Fisetin also has independent neuroprotective mechanisms: it activates ERK and PI3K/Akt signalling in neurons (distinct from its senolytic PI3K inhibition in senescent cells — the context-dependence is mechanistically complex), promotes BDNF expression, inhibits neuroinflammation via NF-κB suppression, and preserves glutathione in neurons. Memory-enhancing effects have been demonstrated in multiple rodent models, and a 2019 Mayo Clinic pilot trial in older adults with Alzheimer's disease showed reduced dementia symptom severity with fisetin supplementation.

How to Take Fisetin

**Senolytic pulse protocol (primary anti-aging use):** 500–1,000 mg/day for 2 consecutive days per month. This pulse dosing approach mirrors the clinical senolytic protocols (similar to dasatinib/quercetin) and allows sufficient drug exposure for senescent cell apoptosis while minimising continuous Bcl-2 inhibition of normal cells. High-fat meals substantially increase fisetin bioavailability — take with avocado, olive oil, or other fat-rich foods. **Continuous neuroprotective / antioxidant use:** 100–200 mg/day with meals. This lower continuous dose provides ongoing flavonoid antioxidant activity and anti-neuroinflammatory effects without the intensity of senolytic pulse dosing. Fisetin bioavailability from food is insufficient for pharmacological effects — a single daily strawberry serving provides ~1.5 mg, far below the 500 mg threshold for senolytic activity. Concentrated supplements are required.

Timing Recommendations

For the senolytic pulse: take both doses across 2 consecutive days (e.g., Day 1 and Day 2 of each month), always with a high-fat meal for maximum absorption. Some protocols use 3 consecutive days quarterly instead of 2 days monthly — both approaches are used in clinical trial settings. For continuous neuroprotective use: any time with a fat-containing meal.

Potential Side Effects & Safety

Fisetin is well tolerated in all completed human studies. GI discomfort may occur at 1,000 mg/day; taking with food resolves most cases. Fisetin inhibits CYP3A4 and may increase plasma concentrations of drugs metabolised by this enzyme. It also has mild antiplatelet activity — relevant before surgery. Its Bcl-2 inhibitory activity (the mechanism of senolytic action) is shared with venetoclax (a cancer drug) — very high doses theoretically could cause thrombocytopaenia (low platelets), though this has not been reported at supplemental doses.

Best Stacks with Fisetin

**Fisetin + quercetin** is the gold-standard natural senolytic combination — broader spectrum senescent cell clearance than either alone, covering different anti-apoptotic pathway dependencies. Adding spermidine (which induces autophagy to clear the cellular debris post-senolysis) on the same or following days creates a comprehensive cellular rejuvenation protocol. The full stack: fisetin (500 mg) + quercetin (1,000 mg) × 2 days/month + spermidine (5–10 mg/day) + NMN (500 mg/day).

Scientific References

All dosage recommendations are grounded in peer-reviewed research.

1. 1
   Fisetin is a senotherapeutic that extends health and lifespan

   EBioMedicine · 2018

2. 2
   The flavonoid fisetin as an intervention for Alzheimer's disease: A systematic review of preclinical and clinical studies

   Nutrients · 2022