Pharmaceuticals

Fisetin

Evidence: animal_plus_anecdotal

Mechanism of Action

Fisetin is a naturally occurring flavonol (3,7,3',4'-tetrahydroxyflavone) found in strawberries, apples, and persimmons that acts as a senolytic by inhibiting the PI3K/Akt/mTOR survival pathway and BCL-2 family anti-apoptotic proteins in senescent cells. It also activates sirtuin-mediated pathways (SIRT1), reduces NF-kB-driven inflammation, and scavenges free radicals as a direct antioxidant. Fisetin demonstrated the most potent senolytic activity among 10 flavonoids screened in a 2018 study, reducing senescent cell burden in aged mice and extending both healthspan and lifespan markers.

Dosing Protocol

Standard: Research indicates 20 mg/kg/day for 2 consecutive days as an intermittent senolytic protocol (approximately 1400-2000 mg for a 70-100 kg individual).

Maintenance: Research indicates 20 mg/kg/day for 2 days, repeated monthly. Some protocols use lower daily doses (100-500 mg/day) for ongoing anti-inflammatory/antioxidant benefits rather than senolytic effect.

Administration: oral

Timing: Take with fat-containing meal for improved bioavailability (fisetin is lipophilic with poor water solubility). Liposomal or lipophilic formulations preferred.

Duration: Intermittent senolytic courses ongoing. Daily low-dose use for antioxidant/anti-inflammatory effects can be continuous.

Notes

Fisetin is the most accessible senolytic compound available without prescription. In the 2018 landmark study by Yousefzadeh et al., fisetin treatment in aged mice reduced senescent cell markers in multiple tissues and extended median and maximum lifespan. Multiple human clinical trials are now underway (AFFIRM-LITE, TROFFi, STOP-Sepsis). Bioavailability is the primary limitation — standard fisetin is poorly absorbed. Liposomal delivery significantly improves plasma levels. Required bloodwork: Basic safety panel (CMP, CBC) at baseline and after first few courses. Senescence biomarkers (p16INK4a) where available. For ongoing low-dose use, annual bloodwork is sufficient. The senolytic protocol (high intermittent dose) is distinct from the daily antioxidant protocol (low continuous dose). Medical supervision recommended for senolytic dosing.

Stacking

  • Dasatinib + Quercetin (complementary senolytic pathways)
  • Spermidine (autophagy induction)
  • Rapamycin (upstream senescence prevention)
  • Omega-3 (anti-inflammatory synergy)

Interactions

  • CYP2C8/CYP3A4 substrates [LOW] — Fisetin may inhibit CYP2C8 and CYP3A4 enzymes at high doses; potential for drug-drug interactions.
  • Anticoagulants [LOW] — Theoretical antiplatelet effect as a flavonoid; monitor if on blood thinners.
  • Chemotherapy agents [MEDIUM] — Fisetin has antitumor properties that may interact with chemotherapy protocols — coordinate with oncologist.

Contraindications

  • Known hypersensitivity to fisetin or flavonoids
  • Pregnancy and breastfeeding (insufficient safety data)
  • Active chemotherapy without oncologist coordination

Side Effects

  • GI discomfort at high senolytic doses
  • Diarrhea
  • Headache
  • Generally well-tolerated — no serious adverse events reported in clinical trials to date

Key Papers

  • 10.1016/j.ebiom.2018.09.015
  • 10.18632/aging.205581
  • 10.1016/j.mad.2024.111932

Source Quality

OTC dietary supplement. Bioavailability is a major concern — standard fisetin has poor absorption (~44% bioavailability). Liposomal formulations or Fisetin with Novusetin are preferred. No pharmaceutical-grade product exists; use third-party tested supplements.

Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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