Fisetin

Senolytic Activity (Cell and Animal Evidence)

In a laboratory screen of 10 flavonoids, fisetin was the most active at killing cultured senescent cells, and intermittent dosing reduced senescent cell burden and extended healthspan markers in aged mice. Whether fisetin clears senescent cells or improves any health outcome in people has not been demonstrated.

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

Proposed antioxidant and anti-inflammatory effects in vascular tissue. Evidence is mechanistic and from animal models; no cardiovascular outcome has been measured in humans.

Supported by Trial 2

Antioxidant Activity

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

Supported by Trial 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.

PI3K/Akt/mTOR Inhibition

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

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.

Nrf2 Activation

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

Fisetin as a Senolytic (Cell Culture and Aged Mice, Not a Human Trial)

PubMed

Study info

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

Population & duration

Cell culture and aged mice.

Findings

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.

Fisetin Human Trials, Ongoing With No Results Yet: Mayo Clinic AFFIRM-LITE

Study info

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

Population & duration

Older adults with frailty.

Findings

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.

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.

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. In laboratory screening it was among the more active flavonoids at clearing senescent ('zombie') cells, and it extended healthspan in aged mice.

What is the recommended dosage of Fisetin?

The clinically studied dose is 100-1,500 mg/day in continuous use; one human RCT used 200 mg/day. The intermittent senolytic regimen (about 1,400-2,000 mg/day) is extrapolated from mice and unvalidated in humans. 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 Preliminary (1 out of 5). It is backed by 2 clinical trials and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 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.

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: Preclinical study in cell culture and aged mice: among 10 flavonoids screened, fisetin was the most active senolytic, and intermittent dosing reduced senescent cell burden and extended median and maximum lifespan in mice. This is animal and in-vitro evidence; no human efficacy outcome has been published.
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 of preclinical literature on fisetin and other natural senolytics as mitochondrial protectants and anti-aging agents. It summarizes cell and animal findings; it is not a human trial and human data remain limited.
Alipour M, Saeidi A, Hejazi K, Laher I, Zouhal H 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 Journal of the International Society of Sports Nutrition. 2026;.PubMedUsed to support: Small randomized controlled trial (44 obese men, 200 mg/day for 12 weeks, four arms combining fisetin and exercise). Fisetin lowered IL-6 and TNF-alpha and improved fasting glucose, insulin and HOMA-IR, mostly as an add-on to exercise. These are inflammatory and metabolic blood markers in one small trial; the study did not measure senescent cell burden, aging, or any longevity or antioxidant clinical outcome.

Benefits

Senolytic Activity (Cell and Animal Evidence)

Anti-Inflammatory Effects

Neuroprotection (Animal Evidence)

Cardiovascular Support

Antioxidant Activity

Mechanism of action

Senolytic Pathway — BCL-2 Family Modulation1

PI3K/Akt/mTOR Inhibition

NF-κB and Inflammatory Pathway Inhibition1

Nrf2 Activation

Clinical trials

Side effects and drug interactions

Common Potential side effects

Important Drug interactions

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Frequently asked questions about Fisetin

Senolytic Pathway — BCL-2 Family Modulation

NF-κB and Inflammatory Pathway Inhibition