Fisetin as a Senolytic Therapy - Quick Reference Sheet

Fisetin as a Senolytic Therapy

Created on 08/09/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 Audit

A cheap plant compound taken in short high-dose bursts to clear worn-out cells that build up with age. The laboratory and animal case is strong; the human case is thin. Small controlled trials in cancer, stroke, and obesity lower blood markers of inflammation, but none measured worn-out cells. Large doses reliably upset the gut. Safety looks good so far. (Full Review)

Protocol

The intermittent high-dose protocol (Mayo Clinic)
20 mg/kg/day, 2 days monthly
Roughly 1,400 mg daily for two days in a 70 kg adult. Senescent cells need weeks to months to reaccumulate, so continuous exposure is unnecessary.
The continuous low-dose protocol
100–200 mg daily
100 mg for seven weeks or 200 mg for twelve weeks. Anti-inflammatory rather than senolytic in intent, and the only schedules with positive randomized evidence.
Best time of day
With the largest fat-containing meal
Morning or midday is preferable to evening on the intermittent protocol. Splitting a large intermittent dose across the day is likely to deliver more.
Time to effect
Inflammatory markers
7–12 weeks
The human trials measured change after seven to twelve weeks of continuous dosing.
Glucose, insulin, and lipid measures
12 weeks
Both randomized trials dosed 200 mg daily for twelve weeks, alone and alongside training.
Senescent-cell clearance
No human data
Animal work implies days for clearance and weeks to months for reaccumulation, an inference from a different species.

Benefits

Contraindications
  • Pregnancy and breastfeeding, without exception
  • Active cancer on treatment (outside a trial, without oncologist agreement)
  • Solid organ transplant recipients on calcineurin inhibitors
  • Bleeding disorder or therapeutic anticoagulation (without INR monitoring)
  • Within two weeks either side of surgery or a planned invasive procedure
  • Severe hepatic impairment (Child-Pugh Class B or C)
  • eGFR below 30 mL/min/1.73 m²
  • Symptomatic orthostatic hypotension, or falls attributable to it
  • Anyone under 18
Key Interactions
  • CYP3A4 substrates with narrow safety margins (tacrolimus, cyclosporine, everolimus, sirolimus, simvastatin, lovastatin, some calcium channel blockers)
  • CYP2C9 substrates, especially warfarin
  • Direct oral anticoagulants (apixaban, rivaroxaban, edoxaban, dabigatran) and antiplatelet agents (clopidogrel, ticagrelor, aspirin)
  • Antihypertensive medications (lisinopril, losartan, amlodipine, hydrochlorothiazide, furosemide)
  • Glucose-lowering medications (metformin, glipizide, insulin, empagliflozin, dapagliflozin)
  • Over-the-counter medications (ibuprofen, naproxen, aspirin, omeprazole, esomeprazole, antacids, caffeine)
  • Supplements with additive senolytic or antiplatelet effects (quercetin, dasatinib, curcumin, high-dose fish oil, ginkgo, garlic extract, vitamin E above 400 international units)
  • Supplements with additive blood-pressure-lowering effects (dietary nitrate, beetroot extract, magnesium, hibiscus, coenzyme Q10, aged garlic extract, potassium salts)
  • Supplements with additive glucose-lowering effects (berberine, chromium picolinate, alpha-lipoic acid, cinnamon extract, high-dose inositol)
  • Supplements that alter absorption or conjugation (piperine, high-dose vitamin C, calcium and magnesium salts, dietary fibre supplements)
  • Other interventions (dasatinib, losartan, platelet-rich plasma injection, chemotherapy, immunotherapy)

Risk & Side Effects

  • High: Absence of long-term human safety data
  • Medium: Gastrointestinal intolerance at senolytic doses; interference with drug metabolism and transport
  • Low: Genotoxicity at supraphysiological concentrations; additive blood-pressure lowering; additive bleeding risk; possible interference with chemotherapy and radiotherapy
  • Speculative: Impaired tissue repair and wound healing; effects of clearing senescent immune cells; weak hormonal activity; hypersensitivity to botanically sourced material

Monitoring

Marker Target Why
High-sensitivity C-reactive protein (hs-CRP) < 0.5 mg/L Primary target; the marker most consistently moved by fisetin in trials
Interleukin-6 (IL-6) < 1.5 pg/mL Upstream driver of C-reactive protein and a core senescence-associated secretory phenotype component
Tumour necrosis factor-alpha (TNF-α) < 2.0 pg/mL Second senescence-associated secretory phenotype component reduced by fisetin in controlled trials
Fasting insulin 2–5 µIU/mL Detects the metabolic effect seen in the controlled trials, earlier than glucose does
Fasting glucose 75–85 mg/dL Confirms the metabolic signal and flags additive low blood sugar if on diabetes medication
Haemoglobin A1c < 5.4 % Three-month average glucose; filters out day-to-day noise in fasting values
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ALT < 20 U/L (women), < 25 U/L (men); AST similar Liver safety; fisetin is hepatically handled and competes for conjugation pathways
Estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73 m² Kidney safety; fisetin conjugates are renally cleared
Complete blood count with platelets Platelets 200–350 ×10⁹/L Bleeding risk surveillance, relevant given flavonol antiplatelet activity
International normalised ratio (INR) Within the individual's prescribed target Detects the warfarin interaction, the fisetin interaction with the most serious potential consequence
Blood pressure, seated and standing < 120/80 mmHg seated, with < 20 mmHg systolic drop on standing Detects additive blood-pressure lowering reported with fisetin
Lipid panel with apolipoprotein B Apolipoprotein B < 80 mg/dL Captures the lipid improvements seen when fisetin was combined with training

Cadence: Baseline within four weeks before the first dose. On a continuous low-dose regimen, inflammatory and metabolic markers at 8 and 12 weeks, then every 6 months. On an intermittent regimen, blood pressure on dosing days of the first two cycles, liver and kidney measures after cycle 3, the full inflammatory and metabolic panel after cycle 6, then every 6 to 12 months. Any change in prescription medication resets this schedule.

Qualitative Assessment

  • Physical function: grip strength, chair-stand time, or gait speed, measured the same way every three months
  • Exercise recovery: time to feel recovered after a hard session, and whether training capacity is trending up or down across cycles
  • Joint stiffness and morning discomfort: the symptom domain with the clearest preclinical rationale
  • Energy and daytime fatigue: rated consistently on a simple scale
  • Cognitive clarity: subjective and unreliable in isolation, but where expectation effects are strongest
  • Gastrointestinal tolerance on dosing days: the most common adverse effect and the one that determines whether a protocol is sustainable