Fisetin (Flavonol · Senolytic · Neuroprotective Antioxidant)
| CAS No. | 528-48-3 |
| Class | Polyphenol · Flavonol · Flavonoid |
| Source | Fragaria ananassa (Strawberry) — highest dietary concentration; also apple, persimmon, grape, kiwi, onion, cucumber |
| Claim strength | Emerging–Moderate |
| Buy from Herbuno | Fisetin 98% Powder (Wax Tree) | High-Purity Isolate | Rhus succedanea → |
Discovery context: Fisetin was first isolated from the 19th century and remained a relatively obscure dietary polyphenol until a 2018 Mayo Clinic publication — by Kirkland, Justice and colleagues — identified it as the most potent senolytic compound among 10 natural and synthetic candidates, producing tissue-wide senescent cell clearance and measurable lifespan extension in aged mice. Structural distinction: It differs from quercetin by the absence of the 5-hydroxyl group on the A-ring, giving it greater lipid solubility and better CNS penetration than most flavonols. Research acceleration: The 2018 paper triggered multiple human Phase 1/2 clinical trials now underway for Alzheimer's disease, COVID-19 long-hauler syndrome, knee osteoarthritis, and frailty in older women — making fisetin one of the fastest-emerging longevity actives. Commercial source: Isolated fisetin at 98% purity is produced from Rhus succedanea (wax tree) or semi-synthetic preparation.
Evidence for Senolytic Activity, Neuroprotection & Antioxidant Support
Senolytic activity: The 2018 Mayo Clinic study demonstrated fisetin at 100 mg/kg cleared senescent cells from adipose, brain, liver, and kidney tissue in aged mice, reduced the SASP (Senescence-Associated Secretory Phenotype), and extended remaining lifespan by ~10%. Fisetin outperformed quercetin, luteolin, curcumin, and several other natural compounds in the same comparison. Multiple human trials are evaluating senolytic activity. Claim strength: Emerging (compelling preclinical; human trial data pending).
Neuroprotection and cognition: Fisetin activates ERK signalling in hippocampal neurons, enhancing long-term potentiation. Rodent models consistently demonstrate memory improvements. A human crossover trial documented improvements in working memory and processing speed in older adults. Claim strength: Emerging–Moderate.
Antioxidant and anti-inflammatory: Scavenges reactive oxygen species, inhibits NF-κB, reduces COX-2 and iNOS. Notably maintains intracellular glutathione levels more effectively than quercetin in several cell models via direct activation of glutathione synthesis. Claim strength: Moderate.
Fisetin 98% Powder (Wax Tree) | High-Purity Isolate | Rhus succedanea →
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Dosage, Bioavailability & Formulator Specification
Senolytic protocol dose: Ongoing human trials use 20 mg/kg body weight for 2 consecutive days, repeated periodically (monthly to quarterly). That is ~1,400 mg/day for a 70 kg adult on pulsed days. Continuous daily dosing studied for neuroprotection and antioxidant applications: 100–500 mg/day.
Bioavailability: Fisetin's higher lipid solubility vs quercetin provides slightly better membrane penetration. Delivery enhancement (liposomal, phytosome, or lipid carrier) meaningfully increases plasma concentrations. Co-administration with food containing fat improves absorption.
Specification: 98% purity isolate is the supplement-grade standard. Confirm HPLC purity and source on the CoA. Dietary fisetin from strawberries (~160 μg/g fresh weight) cannot approach supplement doses — a fact worth noting for transparent consumer communication.
Synergistic pairs: Quercetin (combined senolytic/antioxidant stack), NAD+ precursors (NMN, NR) for comprehensive longevity formulation, pterostilbene (combined sirtuin + senolytic positioning).
Frequently Asked Questions — Fisetin
What makes fisetin a senolytic compound?
Senolytics selectively eliminate senescent cells — aged dysfunctional cells that resist apoptosis and secrete pro-inflammatory SASP factors. Fisetin inhibits pro-survival pathways in senescent cells (including PI3K/AKT) while leaving healthy cells unaffected, triggering selective apoptosis. The 2018 Mayo Clinic study demonstrated this across adipose, brain, liver, and kidney tissue in aged mice.
What is the correct dosing approach for senolytic effects?
Based on mouse-to-human scaling in ongoing trials, the investigational protocol uses 20 mg/kg for 2 consecutive days repeated periodically — not continuous daily supplementation. This pulse design mimics how senolytic drugs are administered clinically to clear accumulated senescent cells. Daily dosing at 100–500 mg is studied for antioxidant and neuroprotective applications independently of the senolytic protocol.
How does fisetin compare to quercetin for healthy aging?
Both are flavonols with antioxidant and anti-inflammatory activity. Fisetin was specifically identified as a more potent senolytic than quercetin in the comparative Mayo Clinic study. Fisetin's greater lipid solubility may provide better CNS penetration. Quercetin has a broader and more established clinical evidence base overall. Many healthy aging formulations combine both.
Can I get enough fisetin from eating strawberries?
No. Strawberries contain approximately 160 μg of fisetin per gram of fresh fruit. Achieving 100–500 mg supplemental doses would require eating 600 g–3 kg of strawberries daily. Isolated supplementation is required for clinically studied doses — a point to communicate transparently in consumer-facing copy.
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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