Fisetin vs Quercetin

Mechanism

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.

Standard Dosing

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).

Timing

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

Cycle Duration

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

Side Effects

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

Contraindications

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

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Mechanism

Quercetin is a flavonoid that inhibits mast cell degranulation and histamine release, functions as a potent senolytic (selectively clearing senescent cells) when combined with dasatinib or fisetin, and activates AMPK and SIRT1 pathways. It inhibits PI3K/Akt/mTOR signaling, suppresses NF-kB, and modulates JAK-STAT inflammatory cascades. As a zinc ionophore, it facilitates zinc entry into cells, which may inhibit viral RNA-dependent RNA polymerase.

Standard Dosing

500-1000mg daily

Timing

With meals for absorption. For senolytic effect: 3-day pulse monthly on empty stomach.

Cycle Duration

ongoing for general use; pulsed monthly for senolytic protocols

Side Effects

• Headache
• Mild GI upset
• Tingling extremities at high doses
• Rare: kidney toxicity at very high doses

Contraindications

• Pregnancy/lactation at high doses
• Concurrent cyclosporine therapy

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