Fisetin
Fisetin (3,3',4',7-tetrahydroxyflavone)
TL;DR
Fisetin is a flavonoid studied as a senolytic, typically 100-1500 mg in intermittent protocols. Animal data are striking; human evidence is still in early trials.
Ideal For
- Adults interested in longevity and senescent cell burden
- People exploring intermittent senolytic protocols
- Those seeking a broad antioxidant flavonoid
Avoid If
- You are pregnant or breastfeeding
- You are on anticoagulants
- You are undergoing chemotherapy, without oncology input
- You are looking for proven human outcomes rather than early-stage research
Frequently Asked Questions
Overview
Fisetin is a flavonol found in strawberries, apples, persimmons and onions, though dietary intake is only a few milligrams a day — far below the doses used in research. It attracted serious attention in 2018 when a Mayo Clinic screen identified it as the most potent senolytic among a panel of flavonoids, and intermittent dosing in aged mice reduced senescent cell burden and extended median and maximum lifespan even when started late in life.
Senescent cells accumulate with age, stop dividing but resist apoptosis, and secrete a mix of inflammatory cytokines and proteases known as the senescence-associated secretory phenotype. Clearing them in animal models improves tissue function across multiple organs. Fisetin appears to work by inhibiting survival pathways, notably PI3K/AKT and BCL-2 family signalling, that senescent cells depend on. It also acts as a broad antioxidant and has neuroprotective effects in models of Alzheimer's disease and stroke.
The honest position on human evidence is that it is preliminary. Mayo Clinic trials are running in frailty, osteoarthritis and post-COVID syndrome, and results so far are limited. Bioavailability is poor — fisetin is rapidly glucuronidated with a half-time measured in a couple of hours — which is why protocols use large intermittent "hit and run" doses over two to three consecutive days rather than daily intake.
How It Works
- Senolytic activity by inhibiting PI3K/AKT and BCL-2 survival pathways in senescent cells
- Reduces the senescence-associated secretory phenotype and its inflammatory output
- Broad antioxidant activity and support of glutathione levels
- Neuroprotective effects in models of neurodegeneration and ischaemia
- Inhibits mTOR signalling, overlapping with other longevity pathways
Quick Facts
- Eliminates senescent cells
- Reduces systemic inflammation
- Neuroprotective effects
- Supports cognitive function
- Potent antioxidant properties
Benefits & Outcomes
Stem Cell Preservation
Fisetin's senolytic effects could plausibly protect the stem cell niche, but human data does not exist.
Lifespan Extension
Fisetin is the leading natural senolytic candidate — clearing zombie senescent cells in animals — with human trials currently underway.
mTOR Regulation
Fisetin is a senolytic flavonoid with impressive mouse data on clearing senescent cells; human trials are underway but results are not yet available.
Protein Folding Support
Fisetin is an early-stage senolytic candidate with no completed human outcome trials.
Sirtuin Activation
Fisetin is a senolytic candidate with essentially no completed human outcome data.
Cellular Senescence Reduction
Fisetin is among the most promising senolytics in animal work, but human trials are still underway.
Neuroprotection
Preclinical neuroprotection is striking; human evidence is absent.
Cognitive Function
Cognitive benefits are limited to animal models.
Antioxidant Protection
Fisetin has strong antioxidant activity in laboratory models but essentially no human data.
Health Concerns Addressed
No linked health concerns yet.
Supporting Research6 studies
The Flavonoid Fisetin Promotes ERK-Dependent Long-Term Potentiation and Enhances Memory
Maher P, Akaishi T, Abe K
Fisetin activated the ERK-CREB signalling pathway in cultured neurons, facilitated long-term potentiation in rat hippocampal slices, and improved object-recognition memory in mice given oral fisetin. Effects were blocked by MEK inhibitors, confirming ERK dependence.
Fisetin: A Dietary Antioxidant for Health Promotion
Khan N, Syed DN, Ahmad N +1 more
Reviews preclinical evidence that fisetin acts as an antioxidant and anti-inflammatory flavonoid, modulating SIRT1, NF-kB, PI3K/Akt and mTOR signalling, with neuroprotective and anticancer activity in cell and animal models. Typical dietary intake is far below the doses used experimentally, and oral bioavailability is poor.
Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh MJ, Zhu Y, McGowan SJ +19 more
Fisetin was the most potent senolytic of the flavonoids tested and extended median and maximum lifespan in aged mice.
Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh MJ, Zhu Y, McGowan SJ +2 more
Fisetin was the most potent senolytic of the flavonoids tested and extended median and maximum lifespan in aged mice.
Senolytic drugs: from discovery to translation
Kirkland JL, Tchkonia T
The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis-driven approach.
Fisetin, a flavonoid with potential health benefits: chemistry, bioavailability and pharmacology
Grynkiewicz G, Demchuk OM
Fisetin has low oral bioavailability and undergoes rapid conjugation, limiting plasma concentrations relative to in vitro active levels.
Safety Information
Potential Side Effects
Well tolerated in the short human trials conducted so far. Mild gastrointestinal upset at gram-level doses. Long-term safety at senolytic doses is genuinely unknown.
Contraindications
Human safety data at senolytic doses are limited to small trials. Avoid in pregnancy and breastfeeding. Discuss with an oncologist before use during cancer treatment, since senolytics interact with apoptotic signalling.
Drug Interactions
- Anticoagulants — flavonoids may have mild antiplatelet effects
- CYP substrates — fisetin inhibits several cytochrome P450 enzymes in vitro
- Chemotherapy agents — theoretical interaction through apoptotic pathways
Pregnancy & Breastfeeding
Pregnancy: insufficient_data
Breastfeeding: insufficient_data
Dosage Guidelines
Dosage Used in Studies
100-500 mg
Best Time to Take
With the largest meal of the day during dosing days
Best Form
A liposomal or phospholipid-complexed preparation, given fisetin's poor baseline absorption
Bioavailability
Flavonoid with poor bioavailability. Found in strawberries, apples, persimmons. Senolytic properties in preclinical studies. Fat enhances absorption. Human efficacy data limited.
Forms Compared
Standard fisetin powder or capsule
Liposomal fisetin
Fisetin with phospholipid complex
Dietary sources
Food & Timing
With a fat-containing meal, which meaningfully improves absorption of this poorly soluble flavonoid
Medical Disclaimer
The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.
Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.