Fisetin & Quercetin
Plant flavonoids studied as senolytics that clear senescent 'zombie' cells and dampen inflammatory signaling.
Summary
Debbie covers fisetin and quercetin mainly as natural senolytics: in mice, high-dose fisetin cleared senescent cells and extended healthspan and lifespan by about 10%, and quercetin is usually paired with the drug dasatinib, with questions about how well quercetin works alone. Human senolytic trials so far are small or early, and a Mayo Clinic phase II trial found no bone-health benefit in postmenopausal women, so she concludes more research is needed and different tissues may need different senolytics. Separately, she presents quercetin as an anti-inflammatory that blocks NLRP3 and lowers TNF-alpha, with small human RCTs showing lower methylglyoxal and reduced pain, stiffness and TNF-alpha in rheumatoid arthritis.
Quercetin is in her stack, taken in place of curcumin when she runs out or rotated with resveratrol; fisetin is not in her January 2026 stack.From My Current Supplement Stack for Longevity
The evidence
-
Human trial
In an RCT in women with rheumatoid arthritis, quercetin at 500 mg/day reduced pain, stiffness, and TNF-alpha levels.
Read the study Discussed in Longevity for the 99% -
Human trial
In a randomized, double-blind, placebo-controlled crossover trial, 160 mg/day quercetin lowered methylglyoxal (an AGE precursor) by an average of 11% after four weeks.
Read the study Discussed in Longevity for the 99% -
Animal
In a 2018 mouse study screening 10 flavonoids, fisetin was the most effective senolytic, clearing 25-50% of senescent cells with a few days of high dosing and extending healthspan and lifespan by about 10%.
Read the study Discussed in Fisetin for Clearing Out Senescent Cells -
Animal
In a 2024 mouse study, intermittent dosing of fisetin significantly improved endothelial function.
Read the study Discussed in Fisetin for Clearing Out Senescent Cells -
Animal
In animals, three-day courses of dasatinib plus quercetin increased cardiac ejection fraction, decreased vascular calcification, and with intermittent dosing improved lung function and reduced pulmonary fibrosis.
-
Animal
Quercetin blocks NLRP3 activation, and in an animal study aspirin plus quercetin reduced NLRP3 inflammasome activation more than either alone.
Doses used in studies
Amounts reported in the research, not dosing recommendations.
| Dose | Context |
|---|---|
| Fisetin 20 mg/kg/day for 3 days per month (about 2 g/day at 50 kg, 4 g/day at 100 kg) | Mayo Clinic fisetin clinical trials, run for five months |
| Fisetin 20 mg/kg/day orally for two days a month | Mayo Clinic trial in older women targeting frailty and inflammation (no results posted at the time) |
| Fisetin 20 mg/kg/day for two days | Phase II trial in 220 elderly patients with sepsis |
| Quercetin 1,250 mg/day + fisetin 1,000 mg/day for 3 consecutive days every 3 weeks | Clinical trial in Egypt with knee pain as primary endpoint (no results posted) |
| Dasatinib 100 mg/day + quercetin 1,000 mg/day for 3 days | Small clinical trial in chronic diabetic kidney disease; fewer senescent cells in fat tissue and blood 11 days later, no effect in skin |
| Dasatinib 100 mg/day + quercetin 1,250 mg/day for 3 days | Small clinical trial in idiopathic pulmonary fibrosis; walking speed and chair-stand times improved |
| Quercetin 500 mg/day | RCT in women with rheumatoid arthritis |
| Quercetin 160 mg/day for four weeks | Crossover RCT on methylglyoxal |
| Quercetin more than 500 mg/day | Meta-analysis of 7 RCTs showing lower blood pressure |
| Luteolin 100 mg + quercetin 70 mg | Supplement studied in children with autism; reduced TNF-alpha |
Cautions
- Talk to your doctor and pharmacist before taking fisetin if you use prescription drugs, especially at high doses; long-term safety beyond months is unknown.
- Fisetin delays clotting time, so caution is warranted for anyone on anticoagulants.
- Fisetin and quercetin inhibit COMT and may cause irritability or anxiety in people with slow COMT variants; fisetin may also interact with drugs metabolized by COMT.
- Anecdotally, high-dose fisetin may cause a flu-like feeling; it lowers blood sugar in animals, so be cautious if prone to hypoglycemia.
- There are open questions about fisetin and kidney issues; talk with your doctor if unsure.
- Quercetin can reduce iron absorption; if you are low in iron, time it away from iron-rich meals or iron supplements.
- Senescence is needed at the right level (e.g., wound healing), so senolytics are pulsed every few months rather than taken continuously.
- Newer studies show possible negative long-term side effects of senolytics like quercetin + dasatinib.