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Fisetin

Also known as: Fisetin, 3,3′,4′,7-tetrahydroxyflavone

Overview

Fisetin is a naturally occurring flavonol-type flavonoid found in various fruits and vegetables, including strawberries, apples, persimmons, onions, and cucumbers. It is primarily studied for its senolytic, antioxidant, anti-inflammatory, neuroprotective, and potential lifespan-extending properties. Fisetin exhibits potent antioxidant activity, selectively eliminates senescent cells, and offers neuroprotective effects through modulation of neuronal pathways. Research is primarily preclinical and early clinical, with robust animal model data and emerging human tissue studies. Clinical trials in humans are limited but underway. Evidence is mainly from well-controlled animal and in vitro human cell studies, with some human observational data. Systematic reviews and meta-analyses in humans are currently lacking.

Benefits

Fisetin demonstrates several evidence-based benefits, primarily observed in preclinical studies. Its senolytic activity reduces cellular senescence markers and the senescence-associated secretory phenotype (SASP) in vascular and adipose tissues, improving arterial function and reducing inflammation in aged mice. Chronic administration in aged wild-type mice extended median and maximum lifespan, improving tissue homeostasis and suppressing age-related pathology. Fisetin also protects dopaminergic neurons in Parkinson’s disease (PD) mouse models, increases striatal dopamine levels, and improves memory consolidation. Anti-inflammatory and antioxidant effects contribute to improved vascular and neuronal health. Some human observational data suggest symptom improvement in PD patients consuming fisetin-rich diets.

How it works

Fisetin acts as a senolytic by selectively inducing apoptosis in senescent cells, reducing SASP factors that promote inflammation and oxidative stress. It improves vascular endothelial function by increasing nitric oxide bioavailability and protects neuronal cells by modulating oxidative stress and neurotransmitter synthesis pathways. Fisetin targets senescent cells expressing p16^Ink4a, modulates Ras-ERK signaling for neuronal differentiation, and affects potassium channels influencing membrane potential. Oral bioavailability is moderate, and intermittent dosing regimens appear effective in animal models, though human pharmacokinetics require further study.

Side effects

Animal studies report few side effects, and fisetin is generally well tolerated in preclinical models. Common, uncommon, and rare side effects are not well documented in humans due to limited human studies. Potential interactions with drugs metabolized by cytochrome P450 enzymes exist due to its flavonoid nature, but specific interactions are not well characterized. Contraindications are not established, and caution is advised in populations with unknown sensitivity. Human data are lacking, and elderly populations may benefit but require clinical validation. More comprehensive safety data from human clinical trials are needed to fully assess the side effect profile.

Dosage

The minimum effective dose in mice was approximately 100 mg/kg body weight with intermittent oral dosing; human equivalent doses are under investigation. Optimal dosage ranges and maximum safe doses are not established for humans. Animal studies used intermittent dosing (e.g., 1 week on, 2 weeks off). Oral supplementation is standard, and bioavailability enhancers may improve efficacy. Flavonoid absorption can be affected by food matrix and metabolism; co-administration with fats may enhance absorption. No specific cofactors are required. Human protocols are not standardized, and further research is needed to determine appropriate dosing guidelines.

FAQs

Is fisetin safe for long-term use?

Animal studies suggest good tolerability, but human safety data are limited. More research is needed to determine the long-term safety profile in humans.

When should fisetin be taken?

Intermittent dosing regimens have shown efficacy in animal models; human protocols are not standardized. Consult healthcare providers for personalized advice.

How soon can benefits be expected?

Vascular benefits were observed within a week post-treatment in mice; lifespan and neuroprotective effects require longer administration. Human timelines are not yet established.

Does fisetin interact with medications?

Potential interactions exist but are not well studied; consult healthcare providers before use, especially if taking other medications.

Is fisetin effective in humans?

Preclinical data are promising; human clinical trials are needed to confirm efficacy and establish appropriate dosing guidelines for human use.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC10928570/ – This animal study focused on vascular function in old mice, using intermittent fisetin dosing. The findings indicated that fisetin decreased vascular cell senescence and SASP-related inflammation, leading to improved endothelial function and nitric oxide bioavailability. This suggests a potential for fisetin to improve vascular health in aging populations, though human studies are needed to confirm these effects.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6197652/ – This preclinical study in progeroid and aged wild-type mice found that fisetin was the most potent senolytic among flavonoids tested. It reduced senescence markers in multiple tissues and extended both median and maximum lifespan, while also improving tissue homeostasis. The study highlights fisetin's potential as a senolytic agent, but translation to human applications requires further investigation.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1015835/full – This article discusses the neuroprotective effects of Fisetin. It highlights that Fisetin increased striatal dopamine levels dose-dependently and protected dopaminergic neurons. The study suggests that Fisetin may improve clinical symptoms in PD patients consuming fisetin-rich diets and enhance memory consolidation.
https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.14060 – This study investigates the senotherapeutic potential of fisetin. The research indicates that fisetin can selectively target and eliminate senescent cells, which accumulate with age and contribute to various age-related diseases. By reducing the burden of senescent cells, fisetin may promote healthier aging and extend lifespan.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.960601/full – This research explores the immunomodulatory effects of fisetin. The study suggests that fisetin can modulate immune responses, potentially reducing inflammation and improving immune function. These findings highlight the potential of fisetin as a therapeutic agent for immune-related disorders.