Quercetin

Mechanism of Action

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.

Dosing Protocol

Notes

Dual utility: daily low-dose for antihistamine/anti-inflammatory effects, monthly pulsed high-dose for senolytic clearance. The senolytic protocol from Mayo Clinic research uses quercetin + dasatinib (prescription). Quercetin + fisetin is the OTC senolytic approach. As a zinc ionophore, it gained attention during COVID. Bromelain co-administration significantly improves absorption.

Stacking

• Zinc
• Vitamin C
• Bromelain (enhances absorption)
• Fisetin
• EGCG

Interactions

• CYP3A4 substrates [MEDIUM] — Quercetin inhibits CYP3A4 — may increase levels of statins, calcium channel blockers, etc.
• Cyclosporine [HIGH] — Quercetin significantly increases cyclosporine bioavailability
• Fluoroquinolone antibiotics [MEDIUM] — Quercetin may compete for DNA gyrase binding sites
• Digoxin [MEDIUM] — May increase digoxin levels via P-glycoprotein inhibition

Contraindications

• Pregnancy/lactation at high doses
• Concurrent cyclosporine therapy

Side Effects

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

Key Papers

• 10.1016/j.ebiom.2019.09.015
• 10.1038/s41591-019-0675-0
• 10.3390/nu12010150

Source Quality

Quercetin phytosome (Quercefit) offers 20x better absorption than standard quercetin. Isoquercetin (enzymatically modified) also has superior bioavailability. Brands: Thorne Quercetin Phytosome, Life Extension Bio-Quercetin.

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