Fisetin
A strawberry flavonoid that is the most potent natural 'senolytic' identified in animal screens, clearing aged cells and extending lifespan in mice; human trials are underway but not yet published.
At a Glance
- Best known for
- Senolytic — selectively clears senescent 'zombie' cells in animal studies, Antioxidant and anti-inflammatory, Neuroprotective in models of Alzheimer's and stroke
- Evidence
- Preliminary
- Typical dose
- 100–250 mg daily
- Type
- Compound
What is Fisetin?
Fisetin is a yellow flavonoid pigment found in strawberries, apples, persimmons, onions, and cucumbers. It belongs to the same flavonol family as quercetin and kaempferol and was studied for decades as a general antioxidant. Interest surged in 2018 when a Mayo Clinic and Scripps screening of ten flavonoids found that fisetin was the most effective at killing senescent cells — damaged cells that stop dividing but linger, secreting inflammatory signals that drive aging and chronic disease. In the same study, giving fisetin to old mice reduced senescent cell burden, lowered inflammation, and extended lifespan by about 10% even when started late in life.
Known Health Benefits
How It Works
Senescent cells survive by over-expressing anti-apoptotic proteins such as BCL-2 and BCL-xL and by activating PI3K/AKT survival signaling. Fisetin appears to tip these cells into apoptosis by inhibiting these survival pathways while leaving healthy cells largely untouched, which is what makes it 'senolytic.' Removing senescent cells reduces the senescence-associated secretory phenotype (SASP), a cocktail of IL-6, IL-1β, and matrix-degrading enzymes that promotes tissue dysfunction. Separately, fisetin activates Nrf2 antioxidant defenses, inhibits NF-κB, and in brain models maintains glutathione levels and protects neurons from excitotoxic damage. It also activates sirtuins and mTOR-related autophagy, overlapping with the pathways targeted by caloric restriction.
What Research Says
The landmark 2018 study in EBioMedicine showed that fisetin was the most potent senolytic among ten flavonoids tested in cell culture, and that treating aged mice with fisetin reduced senescence markers in multiple tissues and extended median and maximum lifespan. These results triggered several human trials at the Mayo Clinic (the AFFIRM and AFFIRM-LITE trials) testing 20 mg/kg for two consecutive days in older adults with frailty, osteoarthritis, and COVID-19-related complications. As of this writing, full results of these trials have not been published, so there is no human evidence yet that fisetin clears senescent cells or improves aging outcomes in people. Older human data are limited to a small trial in colorectal cancer patients on chemotherapy, in which 100 mg daily for 7 weeks reduced inflammatory markers (IL-8, CRP) without apparent harm. Fisetin's safety in humans looks good, but the longevity claims remain extrapolations from mice.
Active Compounds
Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonol related to quercetin
Forms & Bioavailability
Fisetin has poor water solubility and is rapidly conjugated in the gut and liver, so free fisetin blood levels are low and short-lived (half-life under 3 hours in rodents). Much of it circulates as sulfate and glucuronide metabolites, which may retain some activity. Taking it with a fat-containing meal, or using liposomal or phytosome formulations, raises blood levels several-fold. Senolytic protocols use short bursts of high doses specifically because the drug only needs to be present briefly to trigger apoptosis in senescent cells, a 'hit-and-run' approach.
Dosage Guidance
| Use Case | Dosage |
|---|---|
| General antioxidant / anti-inflammatory | 100–250 mg daily |
| Senolytic protocol (experimental) | 20 mg/kg body weight for 2 consecutive days, repeated monthly |
| Inflammatory marker reduction (studied) | 100 mg daily for 7 weeks |
| Cognitive support (animal-based) | 250–500 mg daily |
Always consult a healthcare provider for personalized dosing.
Natural Food Sources
- Strawberries (richest source, about 160 µg per gram)
- Apples (about 27 µg per gram)
- Persimmons
- Onions, cucumbers, lotus root
- Kiwi, grapes, tomatoes (trace)
Potential Side Effects
No significant side effects reported in the few human studies; theoretical GI upset at high intermittent doses
Who Should Avoid It
- Anticoagulant or antiplatelet therapy (warfarin, clopidogrel, aspirin) — additive bleeding risk
- Surgery within 2 weeks
- Medications metabolized by CYP3A4 with narrow therapeutic windows (cyclosporine, tacrolimus, some statins)
- Active chemotherapy — discuss with oncologist, as antioxidants may interfere with some regimens
Pregnancy & Lactation
No safety data exist for fisetin supplements in pregnancy or breastfeeding. Given that it is designed to trigger cell death in certain cells, supplemental doses should be avoided during pregnancy and nursing. Strawberries and other food sources are safe.
Known Drug Interactions
Inhibits CYP3A4 and P-glycoprotein in lab studies; may enhance anticoagulants and antiplatelet drugs; may lower blood sugar additively with diabetes drugs
Evidence Classification
Based on in vitro studies, animal models, pilot trials, or traditional use documentation. Clinical evidence is limited.
Frequently Asked Questions
What is a senolytic and does fisetin actually work as one in humans?
A senolytic is a compound that selectively kills senescent cells — cells that have stopped dividing but resist death and release inflammatory signals. Fisetin is a proven senolytic in mice. Whether it works the same way in people is being tested in clinical trials at the Mayo Clinic, but results have not been published. Right now, the human evidence is limited to safety and inflammatory markers, not senescent cell clearance.
Should I take fisetin daily or in bursts?
Daily low doses (100–250 mg) are used for general antioxidant purposes. Senolytic protocols instead use high doses for 2–3 consecutive days once a month, on the theory that a brief intense exposure is enough to kill senescent cells and that constant exposure is unnecessary. The burst approach is what clinical trials use, but it has not been proven effective or safe for long-term use, and doses of 1000+ mg per day are well above anything tested chronically.
Can I get enough fisetin from strawberries?
Strawberries are the best food source, but at about 16 mg per 100 g you would need to eat several pounds a day to approach even a low supplement dose. Eating strawberries regularly is excellent for overall flavonoid intake, but senolytic-level doses are only achievable with supplements.
How is fisetin different from quercetin?
They are closely related flavonols with overlapping antioxidant and anti-inflammatory effects. In the 2018 senolytic screen, fisetin was more potent than quercetin at clearing senescent cells. Quercetin has far more human trial data for allergies, blood pressure, and exercise performance. Many senolytic formulas include both, sometimes alongside the drug dasatinib in research settings.
References
- Fisetin is a senotherapeutic that extends health and lifespan. Yousefzadeh MJ, Zhu Y, Tripathi U, et al.. EBioMedicine (2018)View study
- Fisetin: a dietary antioxidant for health promotion. Khan N, Syed DN, Ahmad N, Mukhtar H. Antioxid Redox Signal (2013)
- The effects of fisetin supplementation on inflammatory and metabolic markers in colorectal cancer patients: a randomized controlled trial. Farsad-Naeimi A, Alizadeh M, Esfahani A, Darvish Aminabad E. Food Funct (2018)
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This entry is for educational purposes only. It is not medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement regimen, especially if you take medications or have health conditions.