Fisetin is a plant pigment from the flavonol family of flavonoids. Small amounts occur in strawberries, apples, persimmons, grapes, onions and cucumbers. It is sold in the US as a dietary supplement and is promoted as a “senolytic,” a compound meant to clear senescent cells (old, damaged cells that have stopped dividing but keep releasing inflammatory signals).
The most important fact about fisetin is how far the evidence is from the marketing. The senolytic and lifespan findings come from cell culture and mice. One small 2018 mouse study reported a longer lifespan, but a much larger 2024 mouse study run by the NIA’s Interventions Testing Program found no lifespan effect. In people, more than 30 trials are registered on ClinicalTrials.gov. The few with results posted are small, and as of October 2026 none has shown that fisetin slows aging or reduces senescent cells in humans.
This page summarizes what the cell, animal and human studies and the trial registry report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Flavonol (flavonoid polyphenol); 3,3′,4′,7-tetrahydroxyflavone |
| Formula | C₁₅H₁₀O₆, 286.24 g/mol |
| Richest food source | Strawberries (≈160 µg/g in a Japanese food analysis) |
| Route | Oral |
| Doses in human studies | 100–200 mg/day taken daily; or about 20 mg/kg/day for 2–3 days in a row (“intermittent”) |
| Half-life | ≈1.1 h for plain fisetin in 15 healthy adults (one small study) |
| Proposed mechanism | Kills or quiets some types of senescent cells in culture and in mice |
| Lifespan evidence | Mouse only; positive in one small study, not confirmed in a larger one |
| US status | Sold as a dietary supplement; not an FDA-approved drug |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Fisetin’s chemical name is 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one (PubChem). It is close in structure to quercetin, another flavonol sold as a supplement. The only difference is that quercetin carries an extra hydroxyl group at position 5 (Yousefzadeh et al., EBioMedicine 2018).
Dietary sources
A Japanese food analysis, summarized in a 2013 review, measured fisetin in common fruits and vegetables (Khan et al., Antioxid Redox Signal 2013):
| Food | Fisetin content |
|---|---|
| Strawberries | 160 µg/g |
| Apples | 26.9 µg/g |
| Persimmons | 10.5 µg/g |
| Other fruits and vegetables (grape, onion, cucumber) | Within a 2–160 µg/g range |
The same analysis estimated an average intake of about 0.4 mg/day in Japan, far below the 100–200 mg/day or 20 mg/kg doses used in human trials.
Senolytic mechanism
Senescent cells build up with age and in many chronic diseases. They resist programmed cell death (apoptosis) by turning on survival pathways. A senolytic drug briefly switches those pathways off, so the senescent cells die while healthy cells are spared.
Mayo Clinic researchers first reported fisetin as a senolytic in 2017 (Zhu et al., Aging 2017). In cell culture, its effect depended on the cell type:
| Senescent cell type (human, in culture) | Effect of fisetin |
|---|---|
| Umbilical vein endothelial cells (HUVECs) | Selectively killed senescent cells; dividing cells spared |
| IMR90 lung fibroblasts | Not senolytic |
| Primary preadipocytes (fat-cell precursors) | Not senolytic |
The 2018 follow-up screened 10 flavonoids on senescent mouse and human fibroblasts. Fisetin was the most potent of them (Yousefzadeh et al., EBioMedicine 2018). The authors noted some limits:
- In mouse fibroblasts, fisetin lowered senescence markers without clear signs of killing the cells. That pattern fits a “senomorphic” effect (calming senescent cells) as well as a senolytic one.
- In explants of human fat tissue, it reduced senescence only in some cell types.
- The proposed mechanism is blocking the PI3K/AKT/mTOR survival pathway. Fisetin also acts as an antioxidant and reduces inflammatory signals in vitro.
In progeroid mice, senescence markers stayed low during weeks off fisetin, which the researchers described as a “hit-and-run” mechanism. Most human senolytic trials accordingly give large doses on only 2–3 consecutive days instead of a daily dose.
Pharmacokinetics
Fisetin is poorly absorbed. Its water solubility is low (10.4 µg/mL). Animal studies show that it is quickly converted to sulfate and glucuronide conjugates, and gut transporters pump some of it back out (Krishnakumar et al., J Nutr Sci 2022). One active metabolite, geraldol, is a methylated form of fisetin.
The first human pharmacokinetic study was a randomized, double-blind crossover trial in 15 healthy adults aged 22–55. Each took a single dose of plain fisetin (1,000 mg) and, after a 10-day washout, a fenugreek-fiber formulation (FF-20, 1,000 mg delivering 192 mg fisetin) (Krishnakumar et al., J Nutr Sci 2022). The values below were adjusted for the different fisetin content of the two products:
| Parameter (free fisetin in plasma) | Plain fisetin | FF-20 formulation |
|---|---|---|
| Peak concentration (Cmax) | 9.97 ng/mL | 238.2 ng/mL |
| Time to peak | 0.88 h | 1.24 h |
| Half-life (time to half of peak) | 1.14 h | 1.51 h |
| Total exposure (AUC 0–12 h) | 12.67 ng·h/mL | 341.4 ng·h/mL |
Points to keep in mind:
- With plain fisetin, blood levels were only measurable at the 1,000 mg dose. Lower doses could not be quantified.
- Geraldol peaked at about 2.4 times the level of fisetin itself after the plain product.
- The authors work for the formulation’s manufacturer and a supplement retailer. The ≈27-fold advantage has not been tested independently.
Whether blood levels after oral doses reach those that killed senescent cells in culture is not established. In the NIA mouse study, plasma fisetin could not be measured reliably in mice fed fisetin chow (Harrison et al., GeroScience 2024).
Regulatory status
Fisetin is sold as a dietary supplement. It has no FDA-approved drug indication. Mayo Clinic researchers have noted that flavonol senolytics such as quercetin and fisetin are “readily available without US FDA approval” and are already used by healthy older people without trial evidence (Farr et al., Nat Med 2024). Fisetin is not named on the WADA 2026 Prohibited List.
What the research shows
Mouse lifespan: Yousefzadeh 2018 (mouse)
The study that made fisetin popular was done in mice (Yousefzadeh et al., EBioMedicine 2018):
- Progeroid mice. Mice with a DNA-repair defect that makes them age fast were fed chow with 500 ppm fisetin, about 60 mg/kg/day. They showed fewer senescence markers in several tissues.
- Old wild-type mice, short course. Mice aged 22–24 months got 100 mg/kg/day by mouth for 5 days. They had fewer senescent cells in their fat tissue.
- Lifespan. Wild-type hybrid mice were started on 500 ppm fisetin chow at 85 weeks of age, which the authors compared to about 75 human years. Median and maximum lifespan were longer, age-related tissue damage was lower, and ALT (a liver enzyme) and amylase were lower.
The lifespan arm was small, with only 8–9 mice per group. A later summary of the data reported a median lifespan of 30 months on fisetin versus 27 months in controls, with 3 of 8 treated mice outliving all 8 controls (Harrison et al., GeroScience 2024).
Mouse lifespan: the NIA Interventions Testing Program (mouse)
The NIA Interventions Testing Program tests compounds in genetically diverse mice at three sites at the same time. It tested fisetin at 600 ppm in the diet, starting at 20 months of age to match the 2018 study. Fisetin was given either continuously or for 3 days out of every 14 (Harrison et al., GeroScience 2024):
| Group (pooled across 3 sites) | Mice | Median lifespan | Change vs control | p (log-rank) |
|---|---|---|---|---|
| Male control | 292 | 750 days | — | — |
| Male, fisetin 3 days every 2 weeks | 150 | 799 days | +7% | 0.54 |
| Male, fisetin continuous | 142 | 715 days | −5% | 0.85 |
| Female control | 286 | 876 days | — | — |
| Female, fisetin 3 days every 2 weeks | 134 | 871 days | −1% | 0.75 |
| Female, fisetin continuous | 144 | 883 days | +1% | 0.37 |
Neither schedule changed lifespan in either sex. In mice fed fisetin for 2–4 months, p16 (a senescence marker) was not lower in the liver, kidney or brain. The diet contained 99% of the target dose, so a failed diet does not explain the result. The authors note that a different dose, route or mouse strain might give a different result.
Registered human trials
A search of ClinicalTrials.gov in October 2026 found 37 studies listing fisetin as an intervention, including combination products. Most of the dedicated senolytic trials use about 20 mg/kg/day for 2–3 consecutive days. The main ones are:
| Trial | Population | Design and dose | Status (registry) | Results |
|---|---|---|---|---|
| NCT03675724 (AFFIRM-LITE) | Older adults | RCT, 20 mg/kg/day for 2 days vs placebo; n = 40 planned | Enrolling by invitation since 2018 | Not published |
| NCT03430037 (AFFIRM) | Older women | RCT, 20 mg/kg/day for 2 days, in 2 consecutive months; n = 40 planned | Enrolling by invitation since 2018 | Not published |
| NCT04210986 | Knee osteoarthritis | RCT, ≈20 mg/kg/day for 2 days, repeated after 1 month; n = 75 | Completed 2023 | Posted on registry; no journal paper found |
| NCT04771611 (COVFIS-HOME) | Outpatients with COVID-19 | RCT, ≈20 mg/kg/day on days 0–1 and 8–9; n = 55 | Completed 2022 | Posted on registry; no journal paper found |
| NCT04537299 (COVID-FIS) | Nursing home residents with COVID-19 | RCT, same schedule; n = 20 | Terminated for futility | Posted on registry |
| NCT05416515 | Carpal tunnel syndrome | Single arm, 2-day courses over 2 months; n = 40 | Completed 2025 | Posted on registry; no control group |
| NCT05758246 (STOP-Sepsis) | Adults over 65 with sepsis | RCT, 1 or 2 doses of 20 mg/kg vs placebo; n = 220 planned | Recruiting | Not yet available |
Other registered trials are testing fisetin in frailty after childhood or breast cancer, vascular function in older adults, peripheral artery disease, lung disease and sepsis. A Mayo bone trial (NCT04313634) originally had a fisetin arm. That arm was dropped “because of the COVID pandemic and cost issues,” and only the dasatinib plus quercetin results were published (Farr et al., Nat Med 2024).
Bottom line on human trials: the two flagship frailty trials (AFFIRM and AFFIRM-LITE) started in 2018 and still have no published results. No peer-reviewed paper has yet reported a senolytic fisetin trial showing a clinical benefit.
Posted results: knee osteoarthritis
NCT04210986 is the largest placebo-controlled fisetin trial with results. It randomized adults with knee osteoarthritis to fisetin (≈20 mg/kg/day on days 1–2 and 31–32) or placebo and followed them for 12 months. The primary outcome was safety:
| Outcome | Fisetin (n = 34) | Placebo (n = 40) |
|---|---|---|
| Any treatment-emergent adverse event | 28 of 34 | 33 of 40 |
| Serious adverse events | 2 | 2 |
| 6-minute walk at 12 months (adjusted mean) | 544 m | 544 m |
Changes in CRP (an inflammation marker), COMP (a cartilage breakdown marker) and walking distance did not differ significantly between groups at any time point.
Posted results: COVID-19
- COVFIS-HOME (NCT04771611), outpatients. At 60 days, 26 of 27 fisetin patients and 22 of 24 placebo patients had no activity limitations. There were no serious adverse events on fisetin and 2 on placebo. The registry entry does not report a statistical comparison.
- COVID-FIS (NCT04537299), nursing home residents. The trial stopped after 20 participants, when the safety board and the NIA judged further enrollment futile. COVID-19 severity scores were essentially the same in both groups.
Daily low-dose trials
Several small randomized trials used daily doses rather than the intermittent senolytic schedule. They measured blood markers, not senescent cells:
| Trial | n | Dose and duration | Main finding |
|---|---|---|---|
| Colorectal cancer patients on chemotherapy (Farsad-Naeimi et al., Food Funct 2018) | 37 | 100 mg/day for 7 weeks vs placebo | IL-8 fell more than with placebo; hs-CRP and MMP-7 fell within the fisetin group but did not differ significantly from placebo |
| Acute ischemic stroke with clot-busting rt-PA (Wang et al., Clin Appl Thromb Hemost 2019) | 192 | 100 mg/day for 7 days vs placebo, added to rt-PA | Better stroke scores in patients treated 3–5 h after onset; single center, not replicated |
| Men with obesity, with or without training (Alipour et al., Nutrients 2026; Alipour et al., JISSN 2026) | 60 and 44 | 200 mg/day for 12 weeks | Fisetin alone lowered weight vs placebo and IL-6 and TNF-α within the group; the largest changes were with fisetin plus exercise |
These are small trials, each from a single group, with surrogate markers as outcomes. None tested fisetin as a senolytic.
Side effects and risks
What trials report
Across the human studies above, fisetin has not shown a clear safety signal, but the total number of people exposed is small:
- In the osteoarthritis trial, adverse event rates were similar to placebo (28 of 34 vs 33 of 40 participants). The most common events were joint pain, nausea and pain in the limbs, at similar rates in both groups (NCT04210986).
- In the pharmacokinetic study, two of 15 volunteers reported stomach symptoms (bloating, lower appetite). They had them with both products (Krishnakumar et al., J Nutr Sci 2022).
- In COVFIS-HOME, there were no serious adverse events on fisetin (NCT04771611).
Most participants received only a few days of fisetin, and follow-up was a year at most. The long-term safety of repeated high-dose courses is unknown. A 2024 review by researchers running fisetin trials concluded that safety, pharmacokinetics, efficacy and the best dose in humans still need to be established (Tavenier et al., Mech Ageing Dev 2024).
Gaps in the evidence
- No validated way to measure senescent-cell clearance in people. Trials rely on blood markers that are only loosely linked to senescence.
- Product quality. Supplement fisetin is not FDA-reviewed for content or purity. Its poor solubility means the amount absorbed can vary widely between formulations.
- Interactions. No dedicated human drug-interaction studies were found. Trials such as STOP-Sepsis give fisetin to patients on many other drugs, so its interaction profile may become clearer once results are published (Silva et al., Trials 2024).
Populations without data
No trial results are available for pregnancy, breastfeeding or children. Registered trials mostly enroll older adults or people with a specific condition.
Related compounds
- Quercetin is the flavonol paired with dasatinib in the best-known senolytic combination. Fisetin was selected because it looked more potent than quercetin in the 2018 cell screen.
- Urolithin A is another supplement marketed for healthy aging. It works through a different pathway (mitophagy, the recycling of damaged mitochondria). A registered trial in China, NCT06990256, is testing it alongside fisetin.
- Spermidine is a polyamine supplement marketed for longevity. It acts on autophagy (the cell’s recycling system) rather than on senescent cells.
- Rapamycin and metformin are prescription drugs also studied for aging.
Key takeaways
- A food flavonol in supplement doses. Fisetin is found in strawberries and apples, but diets supply about 0.4 mg/day, far below the doses used in human trials.
- Senolytic in some cells, not others. In culture it killed senescent endothelial cells but not senescent lung fibroblasts or fat-cell precursors.
- The lifespan result is mouse-only and was not confirmed. One study of 8–9 mice per group found longer life; the NIA’s study, with 134–150 mice per treated group, found no effect with either schedule.
- Poorly absorbed. In one small human study, plain fisetin was only measurable in blood at a 1,000 mg dose, with a half-life of about 1 hour.
- Human evidence is thin. The flagship frailty trials have not published results since starting in 2018. Posted results from osteoarthritis and COVID-19 trials show no clear benefit over placebo.
- Short-term safety looks acceptable, long-term is unknown. Adverse events matched placebo in the largest posted trial, but few people have been exposed and only for a few days.
Sources
- National Center for Biotechnology Information. PubChem Compound Summary for CID 5281614, Fisetin. PubChem.
- Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013;19(2):151–162. PubMed.
- Zhu Y, Doornebal EJ, Pirtskhalava T, et al. New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463. Aging (Albany NY). 2017;9(3):955–963. PubMed.
- Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18–28. PubMed.
- Harrison DE, Strong R, Reifsnyder P, et al. Astaxanthin 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 used. GeroScience. 2024;46(1):795–816. PubMed.
- Krishnakumar IM, Jaja-Chimedza A, Joseph A, et al. Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study. J Nutr Sci. 2022;11:e74. PubMed.
- Farr JN, Atkinson EJ, Achenbach SJ, et al. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med. 2024;30(9):2605–2612. PubMed.
- Mayo Clinic. AFFIRM-LITE: alleviation by fisetin of frailty, inflammation, and related measures in older adults. ClinicalTrials.gov NCT03675724. ClinicalTrials.gov.
- Mayo Clinic. AFFIRM: alleviation by fisetin of frailty, inflammation, and related measures in older women. ClinicalTrials.gov NCT03430037. ClinicalTrials.gov.
- Steadman Philippon Research Institute. Senolytic drugs attenuate osteoarthritis-related articular cartilage degeneration: a clinical trial. ClinicalTrials.gov NCT04210986 (results posted). ClinicalTrials.gov.
- Kirkland JL (sponsor-investigator). COVFIS-HOME: COVID-19 pilot study of fisetin to alleviate dysfunction and decrease complications. ClinicalTrials.gov NCT04771611 (results posted). ClinicalTrials.gov.
- Mayo Clinic. COVID-FIS: pilot in COVID-19 (SARS-CoV-2) of fisetin in older adults in nursing homes. ClinicalTrials.gov NCT04537299 (results posted). ClinicalTrials.gov.
- Amadio PC (sponsor-investigator). A study of fisetin to treat carpal tunnel syndrome (FITCATS). ClinicalTrials.gov NCT05416515 (results posted). ClinicalTrials.gov.
- Silva M, Wacker DA, Driver BE, et al. Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: study protocol for a multicenter, randomized, adaptive allocation clinical trial. Trials. 2024;25(1):698. PubMed; ClinicalTrials.gov NCT05758246.
- Khosla S (sponsor-investigator). Targeting cellular senescence with senolytics to improve skeletal health in older humans. ClinicalTrials.gov NCT04313634. ClinicalTrials.gov.
- Huazhong University of Science and Technology. Evaluation of urolithin A and fisetin on improving sleep and aging biomarkers. ClinicalTrials.gov NCT06990256. ClinicalTrials.gov.
- Farsad-Naeimi A, Alizadeh M, Esfahani A, Darvish Aminabad E. Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients. Food Funct. 2018;9(4):2025–2031. PubMed.
- Wang L, Cao D, Wu H, et al. Fisetin prolongs therapy window of brain ischemic stroke using tissue plasminogen activator: a double-blind randomized placebo-controlled clinical trial. Clin Appl Thromb Hemost. 2019;25:1076029619871359. PubMed.
- Alipour M, Saeidi A, Hejazi K, et al. The effects of interval resistance-aerobic training and fisetin supplementation on asprosin and selected adipokines in obese men: a double-blind randomized control trial. Nutrients. 2026;18(3):433. PubMed.
- Alipour M, Saeidi A, Hejazi K, et al. 12-weeks fisetin supplementation and interval resistance with aerobic training: changes in Maresin-1 and inflammatory markers in men with obesity: a randomized controlled trial. J Int Soc Sports Nutr. 2026;23(1):2679718. PubMed.
- Tavenier J, Nehlin JO, Houlind MB, et al. Fisetin as a senotherapeutic agent: evidence and perspectives for age-related diseases. Mech Ageing Dev. 2024;222:111995. PubMed.
- ClinicalTrials.gov. Search results for intervention “fisetin” (37 studies, accessed October 2026). ClinicalTrials.gov.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA.