Fisetin
Evidence Fact Sheet
3,3',4',7-tetrahydroxyflavone
Fisetin is a dietary flavonol (3,3',4',7-tetrahydroxyflavone) studied for antioxidant, anti-inflammatory and cellular-senescence ("senolytic") signaling. Human data are limited: one inflammation-marker RCT, a bioavailability/formulation crossover trial, an exercise+adipokine RCT, and an honest null in Gulf War Illness. Sold as a US supplement; no EFSA/ANVISA/China approval.
Also known as: Fisetin · 3,3',4',7-tetrahydroxyflavone · Flavonol polyphenol
Overview
Fisetin (3,3',4',7-tetrahydroxyflavone) is a flavonol polyphenol found in plants such as strawberries and apples, studied as a dietary supplement for cellular-aging and antioxidant research contexts. In research models its proposed mechanisms include senescence-pathway (p53/p21/Bcl-2) signaling, sirtuin (SIRT1/SIRT3) activation, NF-kB suppression, direct ROS scavenging and matrix-metalloproteinase inhibition — most of which is preclinical, with the touted "senolytic" anti-aging data coming from animal and early-phase human work rather than completed healthy-population efficacy trials. Research doses cluster around 100 mg/day used in the single inflammation-marker RCT, with intermittent high-dose senolytic regimens (roughly 20 mg/kg/day for 2 days/month) appearing only in early-phase clinical trials; oral bioavailability is low, motivating formulation work. Regulatory status: marketed in the US as a dietary supplement under DSHEA (structure/function language only) with no NDI/GRAS on record; not an EFSA-authorized claim and potentially Novel Food in the EU; not on the ANVISA positive list in Brazil; and not an approved novel food ingredient in China. Educational evidence summary only — not medical advice or a treatment for any disease.
Mechanism of Action
Senolytic signaling in preclinical models (p53/p21/Bcl-2 pathway; mouse + human-tissue-explant only, not human-validated in vivo) · Sirtuin (SIRT1/SIRT3) activation in research models · NF-kB pathway suppression (mechanistic) · Direct ROS scavenging / free-radical quenching · mTOR modulation (preclinical) · MMP (matrix metalloproteinase) inhibition — observed as reduced MMP-7 in one human RCT
Body systems: Cellular Renewal · Mitochondrial & Cellular Energy · Immune System · Neurological & Cognitive · DNA & Epigenetic
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Fisetin is not characterized as a treatment for any disease.
Inflammatory Markers (Colorectal-Cancer Patients)
RCT supported- n = 37CRC patients · 100 mg/day · 7 wk
- p < 0.04plasma IL-8 reduced
- p < 0.02MMP-7 suppressed
In a placebo-controlled RCT of 37 colorectal-cancer patients on chemotherapy, 100 mg/day fisetin for 7 weeks significantly lowered plasma IL-8 and hs-CRP and suppressed MMP-7 versus baseline, with IL-8 the only marker that differed significantly from placebo between groups. This is the single human efficacy RCT for fisetin and was conducted in a disease population, not healthy people, so it should be read as a research finding on inflammatory markers rather than evidence of a general-population benefit.
Reported effect: IL-8 and hs-CRP reduced significantly in the fisetin group (p < 0.04 and p < 0.01); MMP-7 suppressed (p < 0.02); IL-8 significant vs placebo (p < 0.03); n = 37 (fisetin 18, placebo 19), 100 mg/day x 7 weeks
“37 CRC patients undergoing chemotherapy were assigned to receive either 100 mg fisetin (n = 18) or placebo (n = 19) ... plasma levels of IL-8 and hs-CRP reduced significantly in the fisetin group (p < 0.04 and p < 0.01, respectively) ... fisetin supplementation suppressed the values of MMP-7 levels (p < 0.02) ... significant changes were observed only in IL-8 concentrations in the fisetin group when compared with the placebo group (p < 0.03)”
Source: PMID 29541713 · Farsad-Naeimi 2018 · Food Funct
Oral Bioavailability / Formulation (Healthy Volunteers)
RCT supported- 26.9-foldAUC0-12h increase · p<0.0001
- 23.9-foldCmax increase · p<0.0001
- 15healthy volunteers · crossover
A randomized double-blind crossover study in 15 healthy volunteers compared unformulated fisetin with a galactomannan hybrid-hydrogel formulation (FF-20) at a single 1000 mg dose. The formulation raised systemic exposure roughly 27-fold by AUC and ~24-fold by peak concentration, illustrating that plain fisetin is poorly absorbed and that most of the dose in unformulated products may not reach the bloodstream. This is a pharmacokinetic finding about absorption, not a clinical-outcome benefit.
Reported effect: 26.9-fold greater AUC0-12h (p < 0.0001) and 23.9-fold higher Cmax (p < 0.0001) for FF-20 vs unformulated fisetin; 15 healthy volunteers, single 1000 mg dose
“Pharmacokinetic analysis showed better bioavailability (26.9 times greater area under the curve-AUC0-12 h; p < 0.0001) and better absorption (23.9-fold increase in Cmax; p < 0.0001) in those taking the oral formulation”
Source: PMID 36304817 · Krishnakumar 2022 · J Nutr Sci
Gulf War Illness Symptoms (Honest Negative)
Null / no benefit RCT supported- p = 0.504fisetin low dose · no effect
- p = 0.616fisetin high dose · no effect
- 21veterans completed
In a placebo-controlled crossover screening trial of botanical agents in 21 male veterans with Gulf War Illness, fisetin did not reduce symptom severity at either the lower or higher dose. In the same study resveratrol did outperform placebo, making this a clean honest negative for fisetin specifically and a useful counterweight to senolytic hype.
Reported effect: Fisetin did not reduce symptom severity at either the lower (p = 0.504) or higher (p = 0.616) dosages; 21 male veterans completed the protocol
“Fisetin did not reduce symptom severity at either the lower (p = 0.504) or higher (p = 0.616) dosages. ... Twenty-one male veterans with GWI completed the study protocol”
Source: PMID 33802381 · Hodgin 2021 · Int J Environ Res Public Health
Ischemic Stroke with TPA (Qualitative)
RCT supported- NIHSSlower in delayed-treatment stratum
A double-blind randomized placebo-controlled trial tested fisetin as an add-on to tissue plasminogen activator (tPA) in ischemic stroke. The abstract reports that fisetin was associated with lower NIHSS scores in the delayed treatment-window stratum, with the effect linked to reduced serum MMP-2, MMP-9 and CRP. The abstract does not report sample size, effect size, or p-values, so the magnitude could not be extracted; RCT exists but effect size not extracted.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“Fisetin dramatically improved the treatment outcomes of the patients with stroke in the delayed OTT strata, as revealed by lower NIHSS scores. ... The beneficial effect of fisetin was likely attributable to reduced levels of MMP-2, MMP-9, and CRP in the serum.”
Source: PMID 31434498 · Wang 2019 · Clin Appl Thromb Hemost
Cellular Senescence / Senolytic Biology (Emerging)
Emerging / indexed- phase I/IIonly early human trials
Fisetin is most hyped as a senolytic that clears senescent cells and extends healthspan, but a 2024 narrative review makes clear this rests mainly on in vitro and animal models plus early phase I/II trials, with no completed efficacy RCT in healthy people. The authors explicitly call for further studies to establish safety, pharmacokinetics and efficacy and to identify reliable human outcome measures — so the anti-aging claim should be treated as emerging, not proven.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“examining current evidence from in vitro studies and animal models that investigate fisetin's impact on age-related diseases ... as well as from phase I/II trials in various patient populations ... further studies are needed to establish the safety, pharmacokinetics, and efficacy of fisetin as a senotherapeutic, identify relevant and reliable outcome measures in human trials”
Source: PMID 39384074 · Tavenier 2024 · Mech Ageing Dev
Dosage (research context · not a recommendation)
100 mg/day x 7 weeks was used in the single human efficacy RCT (Farsad-Naeimi 2018, colorectal-cancer patients · inflammation markers, not a healthy-population study). Intermittent senolytic research dosing (~20 mg/kg/day x 2 days/month, i.e. ~1400 mg x 2 days) appears ONLY in early-phase clinical trials and is not a consumer regimen. Oral bioavailability is very low (<5%); a hybrid-hydrogel formulation raised AUC in a healthy-volunteer PK crossover (Krishnakumar 2022). Educational reference only — not a dosing recommendation; no established efficacy dose in healthy people.
Regulatory Status · 4 Markets
- US · FDA
- Marketed as a dietary supplement (multiple brands) but NO published NDI notification or GRAS determination on record — regulatory grey zone under DSHEA; structure/function language only
- EU · EFSA
- No EFSA authorized health claim. Concentrated/purified fisetin extract may trigger the Novel Food Regulation (EU 2015/2283) absent demonstrated pre-1997 EU food-use history; member-state market status varies
- CN · China
- Not approved as a China novel food ingredient; fisetin (concentrated flavonol) is non-traditional and not on the approved food-ingredient inventory — no lawful food/supplement market path in China.
- BR · ANVISA
- NOT on the ANVISA dietary-supplement positive list (IN 28/2018) — market entry would require an innovative-ingredient application (12-24 months); currently not marketable in Brazil
Safety
No formal upper limit established. Short-term human exposure (100 mg/day x 7 wk; and intermittent high-dose 20 mg/kg x 2 days in trials) reported as tolerable with occasional mild GI discomfort, but long-term daily safety beyond ~8 weeks is not established. Very low oral bioavailability (<5%) means actual systemic exposure is limited even at high doses. Not recommended for pregnant/lactating women, children, or people with hepatic/renal impairment (safety data absent). Educational, not medical advice — not a treatment for any disease.
Related
Goals: longevity-stack
Lifestyles: senior-60-plus
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 29541713 · Farsad-Naeimi 2018 · Food Funct — Inflammatory Markers (Colorectal-Cancer Patients)
- PMID 36304817 · Krishnakumar 2022 · J Nutr Sci — Oral Bioavailability / Formulation (Healthy Volunteers)
- PMID 33802381 · Hodgin 2021 · Int J Environ Res Public Health — Gulf War Illness Symptoms (Honest Negative)
- PMID 31434498 · Wang 2019 · Clin Appl Thromb Hemost — Ischemic Stroke with TPA (Qualitative)
- PMID 39384074 · Tavenier 2024 · Mech Ageing Dev — Cellular Senescence / Senolytic Biology (Emerging)
Frequently Asked Questions
1. Is fisetin a proven anti-aging or 'senolytic' supplement?
Not in humans yet. The senolytic and healthspan claims come mainly from in vitro and animal models plus phase I/II trials; a 2024 review (PMID 39384074) explicitly says further studies are needed to establish fisetin's safety, pharmacokinetics and efficacy as a senotherapeutic. There is no completed efficacy RCT in healthy people, so it is best treated as an emerging research area rather than a proven intervention.
2. Why do products use special 'bioavailable' fisetin formulations?
Because plain fisetin is poorly absorbed. In a crossover study of 15 healthy volunteers, a hybrid-hydrogel formulation raised systemic exposure about 26.9-fold by AUC and 23.9-fold by peak concentration versus unformulated fisetin (PMID 36304817). That is a pharmacokinetic (absorption) result, not proof of a clinical benefit — more drug in the blood does not automatically translate into an outcome.
3. Is fisetin approved or regulated as a supplement?
It is marketed in the US as a dietary supplement under DSHEA with structure/function language only, and has no NDI notification or GRAS determination on record. It is not an EFSA-authorized health claim and concentrated extract may fall under EU Novel Food rules; it is not on the ANVISA positive list in Brazil and is not an approved novel food ingredient in China. This page is an educational evidence summary, not medical or dosing advice.
Last evidence review: 2026-06-13