Low-dose fisetin supplementation and chronic inflammation in middle-aged and older adults
A triple-blind randomised controlled trial is investigating whether daily fisetin—a naturally occurring flavonoid from fruits and vegetables—may be associated with reduced blood markers of inflammation in adults aged 50 and older.
Fisetin is a flavonoid compound found in foods like strawberries, apples, and onions that has shown anti-inflammatory, antioxidant, and senolytic effects in laboratory and animal studies, but human evidence remains limited. This triple-blind, randomised, placebo-controlled trial enrolled generally healthy middle-aged and older adults (aged ≥50) to receive either 100 mg of oral fisetin or placebo once daily for 7 weeks.
The primary outcome is change in plasma soluble urokinase plasminogen activator receptor (suPAR)—a biomarker linked to systemic chronic inflammation and age-related disease risk—measured from baseline to week 7. Secondary outcomes include monitoring adverse events and their severity. The study also explores additional inflammatory biomarkers, markers of cellular senescence and aging, frailty, physical function, cognitive function, and subjective health as exploratory measures. Because this is a study protocol article rather than results, specific effect sizes are not yet available; the trial aims to provide evidence on whether low-dose fisetin supplementation is safe and may influence inflammation in humans, addressing a gap where most prior evidence comes from controlled laboratory settings rather than clinical trials.
Fisetin's promise rests on its senolytic properties—the ability to clear senescent cells (damaged cells that accumulate with age and drive inflammation). In animal models and cell cultures, fisetin has demonstrated dose-dependent reductions in pro-inflammatory markers and improved cellular function, but translating these findings to humans requires rigorous testing. This trial's choice of suPAR as the primary endpoint is deliberate: suPAR is a robust predictor of mortality, cardiovascular disease, and frailty risk independent of traditional risk factors, making it a meaningful target. The 7-week duration allows assessment of short-term safety and early biomarker shifts, though longer follow-up would be needed to establish whether inflammation reduction persists or translates to functional benefits. The triple-blind design strengthens confidence in results by preventing bias from researchers, participants, or outcome assessors. Exploratory measures (cognitive and physical function, frailty indices) hint at the researchers' hypothesis that reducing inflammation may improve real-world aging outcomes, not just lab values.
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- Low-Dose Fisetin Supplementation and Its Association With Chronic Inflammation in Middle-Aged and Older Adults: Study Protocol for a Triple-Blind, Randomised, Placebo-Controlled Trial. — Basic & clinical pharmacology & toxicology (Read the original)