Fisetin

Pharmacology & Research

Fisetin is a dietary flavonol that became famous almost overnight for a single idea: that it is a senolytic — a compound that clears the “zombie” senescent cells thought to drive ageing. That reputation rests on one landmark study, and the honest reading of everything since is sobering. The 2018 result was in mice ^{1Reference 1Yousefzadeh MJ et al. · 2018Fisetin is a senotherapeutic that extends health and lifespanView study →}; the gold-standard replication program found no lifespan extension even in mice ^{2Reference 2Harrison DE et al. · 2024AnimalAstaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules usedView study →}; the only published human trial that actually dosed fisetin was null ^{3Reference 3Hodgin KS et al. · 2021RCTA placebo-controlled, pseudo-randomized, crossover trial of botanical agents for Gulf War Illness — resveratrol, fisetin, curcumin, and quercetinView study →}; and the widely-shared “senolytics rebuild bone” headline came from a trial that used a different drug pair (dasatinib + quercetin), not fisetin ^{4Reference 4Farr JN et al. · 2024RCTEffects of intermittent senolytic therapy on bone metabolism in postmenopausal women — a randomized controlled trial (dasatinib plus quercetin)View study →}. Add fisetin’s poor oral bioavailability ^{9Reference 9Shia CS et al. · 2009Metabolism and pharmacokinetics of 3,3’,4’,7-tetrahydroxyflavone (fisetin), 5-hydroxyflavone, and 7-hydroxyflavone and antihemolysis effects of fisetin and its serum metabolitesView study →}, and the gap between the excitement and the human evidence is very wide. This page treats fisetin as a promising preclinical molecule whose human benefits are unproven, because that is what the literature actually supports.

1. Senolytic, healthspan & ageing

The famous claim, and the one to be most careful with. In 2018 Yousefzadeh and colleagues reported that fisetin reduced senescent-cell markers in tissues and extended median and maximum lifespan and healthspan in aged mice — the study that launched fisetin as “the senolytic flavonoid” and set the widely-copied ~20 mg/kg intermittent dosing ^{1Reference 1Yousefzadeh MJ et al. · 2018Fisetin is a senotherapeutic that extends health and lifespanView study →}. Senolytics including fisetin also reduced mortality in a coronavirus model in old mice ^{5Reference 5Camell CD et al. · 2021AnimalSenolytics reduce coronavirus-related mortality in old miceView study →}.

Gap — three hard checks the hype usually skips. First, the NIA Interventions Testing Program — the rigorous, multi-site mouse-lifespan program designed precisely to test such claims — found fisetin did not significantly extend lifespan in either sex ^{2Reference 2Harrison DE et al. · 2024AnimalAstaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules usedView study →}. Second, the only published human trial that actually administered fisetin (a placebo-controlled crossover in Gulf War Illness veterans, n=21) was null at both doses ^{3Reference 3Hodgin KS et al. · 2021RCTA placebo-controlled, pseudo-randomized, crossover trial of botanical agents for Gulf War Illness — resveratrol, fisetin, curcumin, and quercetinView study →}. Third, the celebrated Nature Medicine trial often cited as proof that “senolytics rebuild bone” tested dasatinib + quercetin, not fisetin, and missed its primary endpoint ^{4Reference 4Farr JN et al. · 2024RCTEffects of intermittent senolytic therapy on bone metabolism in postmenopausal women — a randomized controlled trial (dasatinib plus quercetin)View study →} — do not read it as fisetin evidence. Every dedicated human fisetin trial (Mayo frailty/AFFIRM, COVID, chronic kidney disease, osteoarthritis, Alzheimer’s) is ongoing, suspended, terminated, or reported only in the trial registry, with no published positive efficacy result to date ^{6Reference 6Kirkland JL · 2020Senolytic drugs — from discovery to translationView study →}. Score kept low deliberately ^{1,2,3Reference 1Yousefzadeh MJ et al. · 2018Fisetin is a senotherapeutic that extends health and lifespanView study →Reference 2Harrison DE et al. · 2024AnimalAstaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules usedView study →Reference 3Hodgin KS et al. · 2021RCTA placebo-controlled, pseudo-randomized, crossover trial of botanical agents for Gulf War Illness — resveratrol, fisetin, curcumin, and quercetinView study →}.

2. Neuroprotection & cognition

Fisetin has a substantial and consistent preclinical neuroprotection literature — it preserves mitochondrial health and blocks oxytosis/ferroptosis in neuronal models (in this database it is paired with sterubin on the yerba-santa page for exactly this mechanism ^{22Reference 22Goujon M et al. · 2024The neuroprotective flavonoids sterubin and fisetin maintain mitochondrial health under oxytotic/ferroptotic stress in HT22 neuronal cellsView study →}), and reduces multiple physiological risk factors for dementia in animal work reviewed by Maher ^{7Reference 7Maher P · 2024The flavonoid fisetin reduces multiple physiological risk factors for dementiaView study →}.

Gap: there is no published human cognitive trial of fisetin — the neuroprotection story is entirely cell and mouse, and fisetin’s poor brain exposure (a bioavailability problem, below) makes translation uncertain. A mild-Alzheimer’s trial is only recruiting. Preclinical rationale, not human evidence ^{7,22Reference 7Maher P · 2024The flavonoid fisetin reduces multiple physiological risk factors for dementiaView study →Reference 22Goujon M et al. · 2024The neuroprotective flavonoids sterubin and fisetin maintain mitochondrial health under oxytotic/ferroptotic stress in HT22 neuronal cellsView study →}.

3. Anticancer & anti-inflammatory

A large in-vitro/animal literature reports fisetin modulating cancer cell-signalling (PI3K/Akt/mTOR, NF-κB, apoptosis) and dampening inflammatory pathways ^{8Reference 8Farooqi AA et al. · 2021Cancer chemopreventive role of fisetin — regulation of cell signaling pathways in different cancersView study →}.

Gap: no human anticancer or anti-inflammatory efficacy trials exist; this is preclinical chemoprevention pharmacology. Within this database the one concrete isolated-fisetin activity is antifungal — fisetin is the principal antifungal constituent of jatobá xylem sap (MIC <128 µg/mL vs Cryptococcus and dermatophytes) ^{21Reference 21da Costa MP et al. · 2014Antifungal and cytotoxicity activities of the fresh xylem sap of Hymenaea courbaril L. and its major constituent fisetinView study →} — again a laboratory finding. Score reflects mechanism-only evidence ^{8,21Reference 8Farooqi AA et al. · 2021Cancer chemopreventive role of fisetin — regulation of cell signaling pathways in different cancersView study →Reference 21da Costa MP et al. · 2014Antifungal and cytotoxicity activities of the fresh xylem sap of Hymenaea courbaril L. and its major constituent fisetinView study →}.

Mechanisms

Target / pathway	Effect	Relevant to	Evidence
Senescent-cell clearance (senolysis; PI3K/AKT/BCL-2 family)	↓ senescent-cell burden	ageing	animal/in vitro 1Reference 1Yousefzadeh MJ et al. · 2018Fisetin is a senotherapeutic that extends health and lifespanView study →
Oxytosis/ferroptosis inhibition; mitochondrial protection	neuroprotection	neuro	in vitro 22Reference 22Goujon M et al. · 2024The neuroprotective flavonoids sterubin and fisetin maintain mitochondrial health under oxytotic/ferroptotic stress in HT22 neuronal cellsView study →
NF-κB / inflammatory signalling ↓	anti-inflammatory	inflammation	in vitro/animal 8Reference 8Farooqi AA et al. · 2021Cancer chemopreventive role of fisetin — regulation of cell signaling pathways in different cancersView study →
Pro-apoptotic in cancer cells (high concentration)	anticancer	cancer	in vitro 8Reference 8Farooqi AA et al. · 2021Cancer chemopreventive role of fisetin — regulation of cell signaling pathways in different cancersView study →
Topoisomerase I/II inhibition; micronucleus induction	genotoxic potential at high concentration	safety	in vitro 13,14Reference 13López-Lázaro M et al. · 2010The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cellsView study →Reference 14Olaharski AJ et al. · 2005In vitroChromosomal malsegregation and micronucleus induction in vitro by the DNA topoisomerase II inhibitor fisetinView study →
Fungal membrane / ergosterol interference	antifungal	antifungal	in vitro 21Reference 21da Costa MP et al. · 2014Antifungal and cytotoxicity activities of the fresh xylem sap of Hymenaea courbaril L. and its major constituent fisetinView study →

Pharmacokinetics

Fisetin’s pharmacokinetics are the quiet reason its dramatic mouse results are so hard to translate. Oral bioavailability is poor: fisetin has low aqueous solubility, is absorbed modestly and then rapidly conjugated (sulfation and glucuronidation), so it circulates overwhelmingly as conjugates rather than free aglycone ^{9Reference 9Shia CS et al. · 2009Metabolism and pharmacokinetics of 3,3’,4’,7-tetrahydroxyflavone (fisetin), 5-hydroxyflavone, and 7-hydroxyflavone and antihemolysis effects of fisetin and its serum metabolitesView study →}, and it is quickly methylated to an active metabolite, geraldol ^{10Reference 10Touil YS et al. · 2011Flavonoid-induced morphological modifications of endothelial cells through microtubule stabilization — and fisetin disposition/metabolism identifying geraldol as an active metaboliteView study →}, and cleared via bile ^{11Reference 11Huang MC et al. · 2018AnimalPharmacokinetics and biliary excretion of fisetin in ratsView study →}. Plasma residence is short. Critically, there is no published human pharmacokinetic study — the PK data are all rodent, and a dedicated healthy-volunteer PK trial is only recruiting. That matters because the senolytic mouse dose (~20 mg/kg) does not map simply onto human plasma exposure, and the concentrations that drive fisetin’s in-vitro effects are unlikely to be reached in human tissue at tolerable oral doses. Formulation work — liposomal and nanoparticle fisetin — measurably raises bioavailability in animals and is the main avenue being pursued to close the gap ^{12Reference 12Seguin J et al. · 2013Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacyView study →}.

Clinical trials

Fisetin’s human trial record is almost entirely unrealised. The distinction to hold onto is “registry results” (summary data posted to a trials registry) versus a peer-reviewed efficacy publication — fisetin has essentially none of the latter:

Human evidence	Status
Gulf War Illness crossover (dosed fisetin)	Published, null 3Reference 3Hodgin KS et al. · 2021RCTA placebo-controlled, pseudo-randomized, crossover trial of botanical agents for Gulf War Illness — resveratrol, fisetin, curcumin, and quercetinView study →
Mayo frailty/AFFIRM, CKD, COVID, osteoarthritis	Ongoing / suspended / terminated / registry-only — no positive publication 6Reference 6Kirkland JL · 2020Senolytic drugs — from discovery to translationView study →
Alzheimer’s, breast-cancer survivors (TROFFi)	Recruiting; design papers only 23Reference 23Ji J et al. · 2026RCTTROFFi — a phase II randomised controlled trial rationale and design of fisetin for physical function in breast-cancer survivorsView study →
“Senolytics rebuild bone” (Nature Medicine)	Used dasatinib + quercetin, NOT fisetin 4Reference 4Farr JN et al. · 2024RCTEffects of intermittent senolytic therapy on bone metabolism in postmenopausal women — a randomized controlled trial (dasatinib plus quercetin)View study →

Last checked: July 2026.

Isolate vs. Plant Studies

Fisetin is a case where the marketing has sprinted far ahead of the evidence, and the honest cautions are structural. The lifespan claim is mouse-only and partly non-replicated: the 2018 result ^{1Reference 1Yousefzadeh MJ et al. · 2018Fisetin is a senotherapeutic that extends health and lifespanView study →} is genuinely interesting, but the gold-standard NIA program found no lifespan benefit ^{2Reference 2Harrison DE et al. · 2024AnimalAstaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules usedView study →} — a contradiction that belongs on any honest page. The headline human “proof” is a different drug: the Nature Medicine senolytic bone trial used dasatinib + quercetin, not fisetin ^{4Reference 4Farr JN et al. · 2024RCTEffects of intermittent senolytic therapy on bone metabolism in postmenopausal women — a randomized controlled trial (dasatinib plus quercetin)View study →}, and is routinely mis-cited. The dose is unreachable from food: senolytic protocols use gram-scale doses against a dietary intake of ~0.4 mg/day ^{19Reference 19Arai Y et al. · 2000Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentrationView study →}. And structurally fisetin is quercetin minus one hydroxyl — it is 3,3′,4′,7-tetrahydroxyflavone, i.e. quercetin lacking the 5-OH — so much of its cell-signalling behaviour overlaps quercetin’s, and “fisetin-specific” effects should be read with that redundancy in mind ^{17Reference 17Kashyap D et al. · 2019Fisetin and quercetin — promising flavonoids with chemopreventive potentialView study →}. Within this database fisetin is a legitimate constituent of jatobá (the antifungal principle of the xylem sap, not the bark ^{21Reference 21da Costa MP et al. · 2014Antifungal and cytotoxicity activities of the fresh xylem sap of Hymenaea courbaril L. and its major constituent fisetinView study →}) and appears in yerba santa as a neuroprotection partner with sterubin ^{22Reference 22Goujon M et al. · 2024The neuroprotective flavonoids sterubin and fisetin maintain mitochondrial health under oxytotic/ferroptotic stress in HT22 neuronal cellsView study →}; those are occurrence-level facts, not endorsements of the senolytic claims.

Prevalence in Nature

Fisetin is a minor, patchily distributed dietary flavonol. The classic analysis (Arai and colleagues, tabulated by later reviews) makes strawberry the standout by a wide margin — about 160 µg/g (≈16 mg/100 g) — with everything else far lower: apple ~27, persimmon ~11, lotus root ~6, onion ~5, grape ~4, kiwifruit ~2 and peach well under 1 µg/g ^{19,20Reference 19Arai Y et al. · 2000Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentrationView study →Reference 20Khan N et al. · 2013Fisetin — a dietary antioxidant for health promotionView study →}. Even so, these are small numbers: total dietary fisetin intake is on the order of ~0.4 mg/day, and a generous 250 g of strawberries supplies only tens of milligrams ^{19Reference 19Arai Y et al. · 2000Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentrationView study →}. The plant that actually matters for supply is not a food at all — the smoke tree Cotinus coggygria (young fustic), whose heartwood is a historical yellow dye and is far richer in fisetin than any fruit; this is the source commercial fisetin is extracted from ^{18Reference 18Valianou L et al. · 2009Phytochemical analysis of young fustic (Cotinus coggygria heartwood) and identification of isolated colourants in historical textilesView study →}. (The chart above shows foods only; Cotinus would sit far off the top of it.)

The dose gap is the number worth remembering: to reach a single ~1,400 mg senolytic research dose from strawberries (the richest food) you would need on the order of 9 kilograms of strawberries in a day — which is exactly why senolytic protocols use Cotinus-extracted capsules, not fruit. There are no non-plant sources.

Discovery & Synthesis

Fisetin’s name comes from Fisetholz, the German term for young fustic (the wood of Cotinus coggygria, the Eurasian smoke tree / Venetian sumac), a plant used since antiquity as a yellow textile dye — fisetin, with fustin and sulfuretin, is one of its colouring compounds ^{18Reference 18Valianou L et al. · 2009Phytochemical analysis of young fustic (Cotinus coggygria heartwood) and identification of isolated colourants in historical textilesView study →}. The 19th-century first-isolation attribution (usually to Schmid/Herzig) and the Fisetholz etymology are reported from historical and secondary literature rather than a primary indexed source, so they are presented here as reported. Structurally fisetin is 3,3′,4′,7-tetrahydroxyflavone, a flavonol notable for what it lacks: the 5-hydroxyl that most dietary flavonols carry. Compared side by side, quercetin is 3,3′,4′,5,7-pentahydroxyflavone, so fisetin is essentially quercetin minus the 5-OH — a small structural difference invoked to explain differences in metabolism and activity between the two closely related molecules ^{16,17Reference 16Grynkiewicz G · 2019New perspectives for fisetinView study →Reference 17Kashyap D et al. · 2019Fisetin and quercetin — promising flavonoids with chemopreventive potentialView study →}.

Isolated fisetin is a yellow crystalline solid with poor water solubility, which is both why it made a good dye mordant historically and why its bioavailability is a problem pharmaceutically. Commercial fisetin is produced by extraction from Cotinus / Rhus heartwood (and to a lesser extent from other flavonol-rich plants) followed by purification; the bulk of formulation research now focuses on liposomal and cyclodextrin/nanoparticle carriers to raise its absorption ^{12Reference 12Seguin J et al. · 2013Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacyView study →}.

Patents: not yet researched (future patent-loop pass).

Toxicity & Safety

As a flavonol eaten routinely in strawberries, apples and onions, dietary fisetin is a low-toxicity food constituent, and the senolytic clinical trials have used it specifically because it is regarded as well tolerated. The caveats are the familiar flavonol-class, high-concentration ones, and they matter more here because supplement/senolytic doses are so far above dietary intake.

Fisetin shows genotoxic potential in vitro at high concentration. Like other polyhydroxy flavonols it acts as a topoisomerase I/II inhibitor in cells ^{13Reference 13López-Lázaro M et al. · 2010The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cellsView study →} and has induced micronuclei and chromosomal malsegregation in vitro ^{14Reference 14Olaharski AJ et al. · 2005In vitroChromosomal malsegregation and micronucleus induction in vitro by the DNA topoisomerase II inhibitor fisetinView study →} — the class of effect that underlies caution about very high, sustained dosing (and about topoisomerase-active bioflavonoids around pregnancy). It also inhibits CYP drug-metabolising enzymes in vitro, giving a theoretical basis for interactions with medications cleared by those enzymes ^{15Reference 15Václavíková R et al. · 2003AnimalPaclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidantsView study →}. None of these are established clinical harms — they are mechanistic flags — but they are the reason “dietary fisetin is fine; concentrated gram-scale supplements are not well-characterised in humans” is the correct summary. Notably, human safety data remain thin: tolerability is being assessed within the ongoing trials rather than established by a completed safety dataset ^{6Reference 6Kirkland JL · 2020Senolytic drugs — from discovery to translationView study →}.

Dosage

There is no established dose of fisetin. The senolytic research protocol (the “hit-and-run” schedule) uses roughly 20 mg/kg/day for two consecutive days — about 1–1.5 g/day for an adult — repeated intermittently, extrapolated from the mouse work ^{1Reference 1Yousefzadeh MJ et al. · 2018Fisetin is a senotherapeutic that extends health and lifespanView study →}; consumer supplements are typically 100–500 mg/day. All of these sit enormously above the ~0.4 mg/day supplied by diet ^{19Reference 19Arai Y et al. · 2000Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentrationView study →}, and because fisetin’s oral bioavailability is poor and uncharacterised in humans, the actual exposure achieved at any of these doses is uncertain ^{9Reference 9Shia CS et al. · 2009Metabolism and pharmacokinetics of 3,3’,4’,7-tetrahydroxyflavone (fisetin), 5-hydroxyflavone, and 7-hydroxyflavone and antihemolysis effects of fisetin and its serum metabolitesView study →}.

These are descriptive figures, not a recommendation — the honest position is that fisetin’s effective and safe human dose is unknown, because no positive human efficacy trial exists.

References