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 (Yousefzadeh 2018) — 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 — Yousefzadeh 2018 (Mayo Clinic)
PubMed

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
PubMed

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.

More Longevity Ingredients

Cognitive
Longvida® Optimized Curcumin (Verdure Sciences)
Longvida® is a PATENTED CURCUMIN EXTRACT developed by Verdure Sciences using SLCP™ (Solid…
Energy
Nicotinamide Riboside (Niagen®)
Nicotinamide Riboside (NR) is a form of vitamin B3 and a direct precursor to NAD+, the coe…
Muscle & Recovery
Urolithin A (Mitopure® — Mitophagy Activator)
Urolithin A (UA) is a gut microbiome-derived metabolite produced from ellagitannins (found…
Cardiovascular
Ubiquinol (Reduced CoQ10)
Ubiquinol is the REDUCED, electron-rich form of CoQ10 — distinct from ubiquinone (oxidized…

Explore Other Ingredients

Cognitive
Citicoline
Citicoline (CDP-choline) is a naturally-occurring intermediate in phosphatidylcholine bios…
Cognitive
PQQ (Pyrroloquinoline Quinone)
Pyrroloquinoline quinone (PQQ) is a redox-active coenzyme and potent antioxidant naturally…
Cardiovascular
Omega-3 Fatty Acids
Omega-3 fatty acids, primarily eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), an…

Related articles from our blog

📝 Article
🧬 The Longevity Blueprint: Supplements That May Help You Live Better, Longer
We all want to live a long life—but not just longer . We want more years with energy, sharp thinking, and physical vital…
June 06, 2025

Frequently asked questions about Fisetin

What is the recommended dosage of Fisetin?

The clinically studied dose for Fisetin 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 product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Fisetin used for?

Fisetin is studied for senolytic activity (eliminates senescent cells), anti-inflammatory effects, neuroprotection (animal evidence). 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.

Are there side effects from taking Fisetin?

Reported potential side effects may include: Generally well-tolerated at typical doses. GI distress at high HIT doses (1,500-2,000+ mg). Always consult a healthcare provider before starting any new supplement, especially if you have underlying conditions or take medications.

Does Fisetin interact with medications?

Known drug interactions may include: Anticoagulants (warfarin, DOACs) — theoretical bleeding risk at high HIT doses. Antiplatelet drugs — additive bleeding risk at high doses. Consult a pharmacist or healthcare provider if you take prescription medications.

Is Fisetin good for longevity?

Yes, Fisetin is researched for Longevity support. 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.