Fisetin and Quercetin

What it is

Quercetin is a flavonol, a plant compound, and the most abundant dietary flavonol [1]. Fisetin is sold as a supplement, and trials have used 200 mg a day [2]. In this topic, senolytics are drugs that aim to clear senescent cells, old cells that stop dividing and release inflammatory signals [3].

How it might work

Proposed mechanism: senescent cells build up with age and release inflammatory signals that may harm nearby tissue [3]. Dasatinib plus quercetin is proposed to disable the survival networks of these cells, so they die; the drugs clear the body quickly, with elimination half-lives under 11 hours [3].

What the research says

Clearing old cells: nine adults with diabetic kidney disease took dasatinib and quercetin for three days; within 11 days, markers of senescent cells in fat and skin fell. These are lab markers, not health outcomes [3].

Lung scarring: in an open-label pilot of 14 people with idiopathic pulmonary fibrosis, walking distance improved after dasatinib plus quercetin, with no control group [4]. A placebo-controlled pilot of 12 people found no meaningful difference in physical function, but was too small to test this well [5].

Bone: in a phase 2 trial of 60 postmenopausal women, the main bone-breakdown marker did not change overall [6]. An exploratory analysis found a 2.7% rise in radius bone density in women with the most senescent cells [6].

Early Alzheimer's: five people tolerated dasatinib and quercetin for 12 weeks; cognitive scores did not change significantly [7].

Fisetin alone: in a 12-week trial of 60 men with obesity, fisetin at 200 mg a day led to more weight loss than placebo; BMI fell significantly only with training [2]. In 44 men with obesity, fisetin with training changed several inflammation and insulin markers most in the combined group [8].

Blood pressure: meta-analyses of randomised trials find quercetin lowers systolic pressure by about 3 mmHg [9][1]. An umbrella review found a systolic drop of 1.9 mmHg and no diastolic change [10].

Colds: pooled flavonoid supplement trials found about a third fewer upper respiratory infections [11]. The review pooled flavonoids in general and called the sick-day result unclear.

Doses used in studies

Diabetic kidney disease pilot: dasatinib 100 mg and quercetin 1,000 mg on three days [3]. Lung scarring trials: dasatinib 100 mg and quercetin 1,250 mg on three consecutive days a week for three weeks [5]. Fisetin trials: 200 mg a day for 12 weeks [2]. Quercetin blood pressure effects were seen at 500 mg a day or more in one meta-analysis [1].

Safety and interactions

Common side effects in the open-label lung pilot were respiratory symptoms, skin irritation and bruising, and stomach upset [4]. In the placebo-controlled pilot, sleep disturbance and anxiety were more common with dasatinib plus quercetin (4 of 6 people, against none on placebo) [5]. The senolytic trials used dasatinib, a prescription drug, alongside quercetin [5]. No upper intake limit or toxic dose was reported in the studies read. The studies read did not report drug interactions, so these cannot be ruled out. No pregnancy or breastfeeding data were found. The kidney pilot enrolled people with reduced kidney function (eGFR about 27) [3], but its abstract reports no kidney safety results. People on blood pressure medicine should ask a doctor before using quercetin.

Caveats and open questions

Most human senolytic trials are small and open-label, and Mayo Clinic holds senolytic patents with financial interests reported by several authors [3]. Bone density and walking results come from exploratory or uncontrolled analyses and need larger trials [6][4]. A phase 2 fisetin trial in breast cancer survivors is a protocol with results not yet available [12]. The fisetin weight trial describes its men as having obesity, but its entry criteria set BMI below 30 [2].