Home Ingredients Fisetin
LongevityAntioxidant

Fisetin

Evidence Level
Limited
2 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Fisetin is a flavonoid found in strawberries (highest concentration), apples, persimmons, onions, and grapes. Identified as one of the most potent natural senolytics in screening studies — selectively eliminating senescent ('zombie') cells that accumulate with age. Component of intermittent senolytic protocols (typically 20 mg/kg for 2 days monthly). Major Bryan Johnson Blueprint and Mayo Clinic-affiliated longevity research.

Studied Dose 100-1,500 mg/day (continuous) for general antioxidant; HIT PROTOCOL: 20 mg/kg body weight × 2 consecutive days monthly (typical 1,400-2,000 mg × 2 days for senolytic effects)
Active Compound Fisetin (3,3',4',7-tetrahydroxyflavone)

Benefits

Senolytic Activity (Eliminates Senescent Cells)

Yousefzadeh 2018 (Mayo Clinic) screening identified fisetin as the most potent natural senolytic among tested flavonoids. Selectively eliminates senescent ('zombie') cells that accumulate with age and drive chronic inflammation/aging. Animal evidence shows extended healthspan with intermittent fisetin dosing.

Supported by Trial 1

Anti-Inflammatory Effects

Reduces inflammatory cytokine production via NF-κB inhibition, reduces SASP (senescence-associated secretory phenotype) markers. Particularly relevant for chronic age-related inflammation ('inflammaging').

Supported by Trial 1

Neuroprotection (Animal Evidence)

Animal models of Alzheimer's, Parkinson's, and traumatic brain injury show neuroprotective effects. Human translation pending.

Supported by Trial 2

Cardiovascular Support

Antioxidant and anti-inflammatory effects in vascular tissue. Modest clinical evidence; mostly mechanistic and animal data.

Supported by Trial 2, Trial 1

Antioxidant Activity

Direct free radical scavenging and Nrf2 pathway activation — supports endogenous antioxidant defense systems.

Supported by Trial 1

Mechanism of action

1

Senolytic Pathway — BCL-2 Family Modulation

Senescent cells survive via upregulated anti-apoptotic proteins (BCL-2, BCL-xL). Fisetin inhibits these survival pathways, triggering apoptosis selectively in senescent cells. Healthy cells have lower BCL-2 dependency and are spared. Mechanism is dose-dependent and requires high concentrations — basis for HIT (high-intensity intermittent) dosing protocols.

2

PI3K/Akt/mTOR Inhibition

Fisetin inhibits PI3K/Akt/mTOR signaling — pathway involved in cellular senescence maintenance. Reduces SASP factors that drive inflammaging.

3

NF-κB and Inflammatory Pathway Inhibition

Reduces inflammatory cytokine production at multiple levels — TNF-alpha, IL-6, IL-8 reduction in vitro and in vivo.

4

Nrf2 Activation

Activates Nrf2-Keap1 pathway, upregulating endogenous antioxidant enzymes (glutathione synthase, SOD, catalase, NQO1). Adaptive antioxidant response.

Clinical trials

1
Fisetin as Senolytic

Screening study of 10 flavonoid compounds for senolytic activity in vitro and in aged mice. Mayo Clinic.

Cell culture and aged mice.

Fisetin identified as most potent natural senolytic — reduced senescent cell burden in multiple tissues, extended healthspan markers in aged mice. Generated significant clinical interest. Established mechanism for HIT senolytic protocols.

2
Fisetin Human Trials — Mayo Clinic AFFIRM-LITE

Mayo Clinic Phase 2 trial of fisetin (20 mg/kg × 2 days monthly) for frailty in older adults. NCT03675724 + related protocols.

Older adults with frailty.

Trials ongoing; results pending. Notably, this is one of few human trials testing senolytic protocols with established outcome measures. Will provide important data on whether mouse senolytic effects translate to clinical benefit in humans.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated at typical doses.
GI distress at high HIT doses (1,500-2,000+ mg).
Headache.
Bleeding risk theoretical — flavonoids may modestly affect platelets.
Bioavailability very low — most oral fisetin not absorbed; lipid/liposomal formulations improve absorption.
Hypoglycemia in sensitive individuals.
Fatigue / lethargy reported by some during HIT protocols.

Important Drug interactions

Anticoagulants (warfarin, DOACs) — theoretical bleeding risk at high HIT doses.
Antiplatelet drugs — additive bleeding risk at high doses.
Diabetes medications — modest hypoglycemic effect; monitor.
Chemotherapy — theoretical interactions at high doses; consult oncologist.
Immunosuppressants — fisetin's anti-inflammatory effects could theoretically interfere; consult.
Pre-surgery — discontinue HIT protocols 2 weeks before surgery.

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Frequently asked questions about Fisetin

What is fisetin used for?

Fisetin is a flavonoid found in strawberries and other fruits, studied for antioxidant and brain-health support and, more recently, as a senolytic, a compound that may help clear aged senescent cells, which is of interest in longevity research.

What is fisetin's role in longevity research?

Fisetin is being studied as a senolytic that may help remove senescent (aged, dysfunctional) cells, which accumulate with age. This research is early and mostly preclinical, so its anti-aging use is promising but not yet proven in humans.

How much fisetin should I take?

Longevity enthusiasts sometimes use higher intermittent doses (periodic high-dose protocols studied in research), while general antioxidant use is lower. Optimal human dosing is not established; follow product labeling and consider professional guidance.

Is fisetin safe?

Fisetin from foods is very safe, and supplements appear generally well tolerated short-term. Long-term and high-dose human safety data is limited, so use thoughtfully and check with a doctor, especially if on medication.

What is Fisetin?

Fisetin is a flavonoid found in strawberries (highest concentration), apples, persimmons, onions, and grapes. Identified as one of the most potent natural senolytics in screening studies — selectively eliminating senescent ('zombie') cells that accumulate with age.

What is the recommended dosage of Fisetin?

The clinically studied dose is 100-1,500 mg/day (continuous) for general antioxidant; HIT protocol: 20 mg/kg body weight × 2 consecutive days monthly (typical 1,400-2,000 mg × 2 days for senolytic effects) Always follow the product label and check with a healthcare provider for personal advice.

Is Fisetin safe, and does it have side effects?

For most healthy adults, Fisetin is well tolerated at studied doses. Reported effects can include: Generally well-tolerated at typical doses. GI distress at high HIT doses (1,500-2,000+ mg). It may also interact with some medications. Fisetin is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Fisetin interact with any medications?

Possible interactions include: Anticoagulants (warfarin, DOACs) — theoretical bleeding risk at high HIT doses. Antiplatelet drugs — additive bleeding risk at high doses. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Fisetin?

NutraSmarts rates the evidence for Fisetin as Limited (2 out of 5). It is backed by 2 clinical trials and 2 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(2 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ Fisetin is a senotherapeutic that extends health and lifespan EBioMedicine. 2018;36:18-28. doi: 10.1016/j.ebiom.2018.09.015.PubMedUsed to support: Landmark preclinical study demonstrating fisetin is the most potent natural senolytic among 10 flavonoids tested, reducing senescent cell burden and extending healthspan and lifespan in mice; backs 'Senolytic Activity (Eliminates Senescent Cells)' and 'Anti-Inflammatory Effects' (animal/in vitro evidence — human clinical trials are ongoing but not yet published with efficacy outcomes).
  2. Deledda A, Giordano E, Velluzzi F, Flore G, Franceschelli S, Speranza L, Ripari P Mitochondrial Aging and Senolytic Natural Products with Protective Potential International Journal of Molecular Sciences. 2022;23(24):16219. doi: 10.3390/ijms232416219.PubMedUsed to support: Review article summarizing preclinical evidence for fisetin and other natural senolytics as mitochondrial protectants and anti-aging agents; backs 'Senolytic Activity', 'Anti-Inflammatory Effects', and 'Neuroprotection (Animal Evidence)' (review of preclinical literature; human data remains limited).