Fisetin Senolytic Reduction of Atrial Arrhythmia Susceptibility
Evidence boundary: Preclinical (aged rabbit) + associative human tissue data. No RCT for AF indication. Supplement doses likely below studied cardiac dose. Route of administration in key study is undisclosed — critical dose translation gap.
TL;DR
Fisetin, a natural flavonol, reduced induced atrial fibrillation (AF) in aged rabbits by selectively eliminating senescent atrial cells. No human clinical trial data exist for this specific indication. Wearable AF burden monitoring is the most actionable Vitals angle, but requires human clinical oversight.
Index Study
PMID 41513056 / PMC13075518 — Sengun et al., Heart Rhythm, 2026 (Brown University)
- Aged rabbit atria (≥4 years), fisetin 20 mg/kg × 2 cycles
- Inducible AF: 100% → 20%; Spontaneous AF: 40% → 0%
- Reentry activity decreased; no contractile impairment
- Human arm (n=265): SASP genes correlated with LA diameter; SA-β-Gal+ counts NOT significantly different AF vs non-AF
Evidence Grades
| Claim | Grade |
|---|---|
| Fisetin has senolytic activity | Confirmed |
| Reduces inducible AF in aged rabbits | Supported |
| Preserves contractile function | Supported |
| Human RCT for AF indication | Gap |
| Long-term cardiac senolytic safety | Gap |
Vitals Angle
Wearable monitoring (investigational):
- HRV trends, AF burden, atrial run frequency via Oura/Whoop/Apple Watch
- 1/3/6-month post-senolytic surveillance protocol
- SASP biomarker panel as senolytic efficacy proxy
- Human signoff required before protocol recommendation
Key Unknowns
- Route of administration in Brown study (oral vs IP — undisclosed)
- Human dose equivalence unestablished
- Established vs preventive AF effect unknown
- No comparison to standard AF care
Cross-Links
- Fisetin (existing general fisetin note — if exists)
- Atrial Fibrillation (standard management)
- Senolytic Therapy (class-level note)
- GLP-1 and Body Composition (adjacent: muscle preservation during weight loss)
Source
- Batch:
batch-117-2026-04-24 - Monograph:
skills/knowledge-base/fisetin-atrial-fibrillation-senolytic/fisetin-atrial-fibrillation-senolytic.md - Claim Registry:
skills/knowledge-base/fisetin-atrial-fibrillation-senolytic/CLAIM-REGISTRY.md