Fisetin is a plant-based flavonoid found naturally in strawberries, apples, and other fruits and vegetables. It functions as a potent antioxidant and senolytic compound, meaning it may help remove aged, dysfunctional cells from the body. Research suggests fisetin supports healthy aging and brain health, though most evidence comes from animal studies with limited human clinical trials.
💡 What You Need to Know Right Away
- Fisetin was identified as the most potent senolytic among 10 flavonoids tested, extending both median and maximum lifespan in aged mice[Evidence: A][1]
- Intermittent fisetin supplementation improved physical function and decreased cellular senescence comparable to genetic senescent cell clearance[Evidence: B][6]
- In colorectal cancer patients, 100 mg fisetin daily for 7 weeks significantly reduced inflammatory markers IL-8 and C-reactive protein[Evidence: B][14]
- Fisetin's antioxidant properties diminish oxidative stress, reduce reactive oxygen species production, and combat neuroinflammation[Evidence: C][7]
If you have been researching longevity supplements, you have likely encountered fisetin. This naturally occurring flavonoid has captured the attention of aging researchers worldwide, with studies exploring its potential to clear damaged cells and support healthy aging.
It is common to feel uncertain when evaluating a newer supplement with promising but limited human data. You want to make informed decisions about your health without being misled by exaggerated claims. This guide examines what the science actually shows about fisetin's benefits, proper dosage, safety considerations, and where the research gaps remain. We will help you understand both the potential and the limitations of current evidence.
❓ Quick Answers
What is fisetin?
Fisetin is a naturally occurring flavonoid, a type of plant polyphenol with antioxidant properties. It is found in various fruits and vegetables including strawberries, apples, and persimmons. Research has identified fisetin as a senolytic agent, meaning it may help clear senescent (aged, dysfunctional) cells from the body.[Evidence: A][1]
How does fisetin work?
Fisetin works through multiple mechanisms. As a senolytic, it targets and helps eliminate senescent cells that accumulate with age. It also reduces oxidative stress, decreases reactive oxygen species production, and combats neuroinflammation through its antioxidant pathways.[Evidence: C][7] Additionally, fisetin modulates cell signaling through PI3K/Akt/mTOR, NF-κB, and MAPK pathways.[Evidence: D][19]
What foods are high in fisetin?
Fisetin is found naturally in several fruits and vegetables. Strawberries are considered the richest dietary source. Other sources include apples, persimmons, onions, and grapes. However, the concentrations in food are relatively low, making it challenging to achieve therapeutic doses through diet alone.[Evidence: C][11]
What are the benefits of fisetin?
Research suggests fisetin may support cellular health through senolytic activity, provide neuroprotective effects by reducing oxidative stress and neuroinflammation, and offer anti-inflammatory benefits. In one clinical trial, fisetin significantly reduced inflammatory markers in colorectal cancer patients.[Evidence: B][14] Animal studies show lifespan extension and improved physical function.[Evidence: A][1]
How much fisetin should I take daily?
Clinical trials have used varying doses. A colorectal cancer study used 100 mg daily for 7 weeks.[Evidence: B][14] A biological aging pilot study used 500 mg daily for one week per month over six months.[Evidence: B][4] Optimal dosing has not been established. Consult a healthcare provider for personalized guidance.
Is fisetin safe?
Current clinical trials report no serious adverse effects at tested doses. A colorectal cancer trial using 100 mg daily for 7 weeks found fisetin was well-tolerated.[Evidence: B][14] However, long-term safety data beyond 12 weeks in humans is limited. Fisetin inhibits the CYP2C8 enzyme, which may affect how certain medications are metabolized.[Evidence: C][10]
Does fisetin really work?
Fisetin shows strong effects in animal studies, extending healthspan and lifespan in aged mice.[Evidence: A][1] Human evidence is more limited. NIH-funded trials are examining fisetin for various conditions.[Evidence: B][3] The compound shows promise, but more human clinical data is needed to confirm efficacy for specific health outcomes.
Can you take fisetin every day?
Some protocols use daily dosing (100-500 mg), while others use intermittent approaches (higher doses for 2-3 consecutive days monthly). The intermittent approach mimics the "hit-and-run" senolytic mechanism studied in animal research.[Evidence: A][1] Optimal dosing frequency has not been established in humans. Consult a healthcare provider before starting any protocol.
🔬 How Does Fisetin Work?
Understanding how fisetin works requires looking at a fundamental process called cellular senescence. As we age, some of our cells enter a state where they stop dividing but refuse to die. Think of these senescent cells as retired workers who stay in the office, taking up space and spreading negativity. They release inflammatory compounds that damage neighboring healthy cells, contributing to aging and age-related diseases.
Fisetin acts as a senolytic agent, essentially a specialized cleanup crew that identifies and removes these dysfunctional cells. In a landmark study comparing 10 different flavonoids, fisetin emerged as the most potent senolytic, effectively clearing senescent cells and extending both median and maximum lifespan in aged mice.[Evidence: A][1]
Beyond its senolytic activity, fisetin works through multiple molecular pathways. Imagine fisetin as a master dimmer switch that can turn down inflammatory signals throughout the body. It modulates key signaling cascades including PI3K/Akt/mTOR, NF-κB, and MAPK pathways.[Evidence: D][19] These pathways control cell growth, survival, and inflammatory responses.
The compound's antioxidant properties help neutralize reactive oxygen species (ROS) and reduce oxidative stress. Research demonstrates fisetin diminishes ROS production, decreases neurotoxicity, and combats neuroinflammation.[Evidence: C][7] This multi-pathway approach may explain why fisetin shows benefits across different organ systems.
In neuroprotection research, fisetin has been shown to enhance learning and memory while decreasing neuronal cell death and suppressing oxidative stress in the brain.[Evidence: C][11] Animal studies demonstrate fisetin supplementation improves physical function and decreases cellular senescence markers in skeletal muscle, with effects comparable to genetic clearance of senescent cells.[Evidence: B][6]
The compound also influences autophagy, the cellular recycling process, and affects Nrf2 signaling, which regulates antioxidant defenses. In cancer cell studies, fisetin reduces autophagy and suppresses Nrf2, increasing programmed cell death (apoptosis) through ROS elevation.[Evidence: B][15]
📊 Dosage and How to Use
Determining the right fisetin dosage is challenging because optimal protocols have not been established through large-scale human trials. Current evidence comes from smaller studies using different dosing strategies. Below is a summary of dosages used in clinical research.
| Purpose/Condition | Dosage | Duration | Evidence |
|---|---|---|---|
| Inflammatory reduction (colorectal cancer patients) | 100 mg/day | 7 weeks | [B][14] |
| Biological aging reduction | 500 mg/day (1 week per month) | 6 months | [B][4] |
| Sepsis prevention (elderly) | 20 mg/kg body weight | Single dose or 2 doses | [B][2] |
Important notes about dosing:
- The 20 mg/kg protocol translates to approximately 1,400 mg for a 70 kg (154 lb) adult
- The intermittent high-dose approach mimics the "hit-and-run" senolytic mechanism from animal research
- Daily low-dose protocols (100-500 mg) may provide consistent antioxidant support
- No single "optimal" dose has been established for general wellness
Bioavailability Considerations
A significant challenge with fisetin is its poor bioavailability. The compound has limited water solubility and poor absorption in its standard form.[Evidence: D][13] Enhanced formulations may address this issue. A randomized, double-blind study found that a novel hydrogel formulation (FF-20 with fenugreek galactomannans) significantly improved fisetin absorption compared to unformulated fisetin in healthy volunteers.[Evidence: B][9]
⚠️ Risks, Side Effects, and Warnings
Side Effects
Clinical trials to date report no serious adverse effects at tested doses. In the colorectal cancer study using 100 mg daily for 7 weeks, fisetin supplementation was well-tolerated.[Evidence: B][14] However, comprehensive side effect data from large-scale trials is not yet available.
Drug Interactions
Fisetin and its methylated metabolite geraldol selectively inhibit CYP2C8 in human liver microsomes. The equilibrium dissociation constant was 4.1 μM for fisetin and 11.5 μM for geraldol.[Evidence: C][10] CYP2C8 metabolizes several medications including:
- Repaglinide (diabetes medication)
- Paclitaxel (chemotherapy drug)
- Amodiaquine (antimalarial)
- Cerivastatin (cholesterol medication, withdrawn)
If you take medications metabolized by CYP2C8, consult your healthcare provider before using fisetin supplements.
Special Populations
Pregnancy: Animal studies examined gestational fisetin intake at 10-50 mg/kg doses during pregnancy, finding the lower dose more effective for neuroprotection against mercury toxicity in offspring.[Evidence: C][18] However, human pregnancy safety data is not available. Pregnant women should consult their healthcare provider before use.
Vascular conditions: Animal research suggests fisetin may reduce inflammatory markers and oxidative stress in deep vein thrombosis models.[Evidence: C][17] However, if you have bleeding disorders or are on blood thinners, consult your doctor before use.
Contraindications
- Known allergy to fisetin or related flavonoids
- Concurrent use of CYP2C8-metabolized medications without medical supervision
- Scheduled surgery (discontinue at least 2 weeks prior due to potential effects on blood parameters)
🥗 Practical Ways to Use Fisetin
How to Use This in Your Daily Life
Scenario 1: Anti-Inflammatory Support
- Dose: 100 mg daily[14]
- Duration: 7 weeks[14]
- Population: Adults seeking anti-inflammatory benefits
- Timing: With meals to improve absorption
- What to track: Inflammatory markers (CRP, IL-8 if testing available), subjective inflammation symptoms
- Expected results: Significant reductions in IL-8 and C-reactive protein observed in clinical trial[14]
Scenario 2: Intermittent Senolytic Protocol
- Dose: 500 mg daily for one week per month[4]
- Duration: 6 months[4]
- Population: Adults over 50 interested in longevity optimization
- Timing: With a fat-containing meal
- What to track: Biological age markers if available, energy levels, physical function
- Expected results: Variable individual response (4/10 reduced biological aging, 5/10 increased, 1/10 no change in pilot study)[4]
Practical Integration
Take fisetin with meals containing healthy fats to potentially improve absorption. Standard fisetin has poor water solubility and limited bioavailability.[Evidence: D][13] Enhanced formulations using nanodelivery methods or hydrogel technology may improve absorption.[Evidence: C][8][9] Store supplements in a cool, dry place away from direct sunlight.
Common Mistakes to Avoid
- Expecting immediate results: Senolytic effects are subtle and occur over weeks to months. Studies used 7-week to 6-month durations[14][4]
- Inconsistent dosing: Clinical trials used consistent daily or weekly protocols. Sporadic use may not achieve intended benefits
- Ignoring bioavailability: Standard fisetin has poor absorption. Consider enhanced formulations or take with fats
- Not tracking response: Individual responses vary significantly. Monitor your own markers and symptoms
⚖️ Fisetin vs. Quercetin
Fisetin and quercetin are both flavonoids with senolytic properties, but they have different research profiles and characteristics. Both compounds are found in fruits and vegetables and share similar mechanisms, yet research suggests they may have distinct strengths.
| Feature | Fisetin | Quercetin |
|---|---|---|
| Senolytic Potency | Most potent among 10 flavonoids tested[1] | Established senolytic, often combined with dasatinib |
| Research Depth | Emerging (fewer human trials) | More extensive research history |
| Primary Food Sources | Strawberries, apples, persimmons | Onions, apples, berries, capers |
| Bioavailability | Low (poor water solubility)[13] | Low (similar challenges) |
| Typical Study Doses | 100-500 mg daily or 20 mg/kg intermittent | 500-1000 mg daily or higher intermittent |
| Epigenetic Effects | May mitigate negative effects of D+Q[5] | Used in D+Q combination protocols |
Can You Take Both?
Research has examined combinations of dasatinib, quercetin, and fisetin (DQF). One longitudinal study found that fisetin addition to the dasatinib-quercetin combination mitigated some negative effects on epigenetic age acceleration markers.[Evidence: B][5] However, optimal combination protocols have not been established. Consult a healthcare provider before combining senolytics.
What The Evidence Shows (And Doesn't Show)
What Research Suggests
- Fisetin is the most potent senolytic among 10 flavonoids tested, demonstrating ability to clear senescent cells and extend lifespan in aged mice (Level A evidence, n=multiple animal cohorts)[1]
- In colorectal cancer patients (n=37), 100 mg fisetin daily for 7 weeks significantly reduced inflammatory markers IL-8 and C-reactive protein[14]
- Intermittent fisetin supplementation improves physical function and decreases cellular senescence markers comparable to genetic senescent cell clearance in animal models[6]
- In stroke patients, fisetin extended the therapeutic window for rt-PA treatment and reduced inflammatory markers MMP-2, MMP-9, and CRP[12]
- Multiple mechanistic studies confirm fisetin's antioxidant, anti-inflammatory, and neuroprotective properties through established molecular pathways[7][19]
What's NOT Yet Proven
- Optimal human dosage: Studies used 100 mg to 20 mg/kg with varying protocols. No consensus on best dose for general wellness
- Long-term safety: The longest human trial was 7 weeks[14]. Safety beyond 12 weeks is unknown
- Lifespan extension in humans: Only demonstrated in animal models. No human longevity data exists
- Consistent efficacy: Pilot study showed highly variable individual responses (only 4/10 showed biological age reduction)[4]
- Populations not studied: Children, lactating women, and individuals with specific health conditions have not been included in trials
- Cognitive outcomes: No human trials specifically measuring memory, focus, or cognitive function
Where Caution Is Needed
- Drug interactions: Fisetin inhibits CYP2C8 enzyme at 4.1 μM. This may affect medications including repaglinide, paclitaxel, and others[10]
- Variable response: The biological aging pilot study showed only 40% of participants experienced reduced biological aging, while 50% actually showed increased biological aging[4]
- Bioavailability challenges: Standard fisetin has poor water solubility and limited absorption. Therapeutic efficacy may depend on formulation[13]
- Animal-to-human translation: Strong animal results do not guarantee human efficacy. Many compounds effective in mice fail in human trials
Should YOU Try This?
Best suited for: Adults over 50 interested in longevity optimization who understand the evidence is preliminary, have consulted with a healthcare provider, are not taking CYP2C8-metabolized medications, and can commit to consistent protocols used in research.
Not recommended for: Pregnant or breastfeeding women (no human safety data), individuals on medications metabolized by CYP2C8, those with scheduled surgeries (discontinue 2 weeks prior), anyone seeking guaranteed results or immediate effects.
Realistic timeline: Clinical trials used 7 weeks to 6 months to observe effects[14][4]. Benefits are subtle and often measured by biomarkers rather than subjective feeling. Individual responses vary significantly.
When to consult a professional: Before starting any fisetin protocol, especially if taking medications, have underlying health conditions, are over 65, or want guidance on dosing and monitoring.
Frequently Asked Questions
What are fisetin side effects?
Clinical trials have not reported serious adverse effects at tested doses. The colorectal cancer trial using 100 mg daily for 7 weeks found fisetin well-tolerated with no significant side effects noted. However, comprehensive side effect data from large-scale, long-term human trials is not yet available. Potential concerns include interactions with medications metabolized by CYP2C8 and theoretical effects on blood parameters. Monitor for any unusual symptoms and discontinue if adverse reactions occur.
Is fisetin better than quercetin?
Fisetin was identified as the most potent senolytic among 10 flavonoids tested in laboratory and animal studies. However, 'better' depends on your goals and circumstances. Quercetin has a longer research history and more extensive human trial data. Some research suggests fisetin may complement quercetin-based protocols by mitigating certain negative effects. The compounds have different strengths, and neither has been definitively proven superior for human health outcomes.
How long does fisetin take to work?
Timeline varies by outcome and has not been precisely established. Clinical trials observed effects at different timepoints. The colorectal cancer trial measured significant inflammatory marker reductions after 7 weeks of daily 100 mg dosing. The biological aging pilot study used 6 months of intermittent dosing (one week per month). Senolytic effects targeting cellular senescence may require weeks to months. Individual responses vary significantly, and many benefits may be measured by biomarkers rather than subjective feeling.
Is fisetin good for your brain?
Research supports fisetin's neuroprotective potential through multiple mechanisms. Studies demonstrate fisetin enhances learning and memory, decreases neuronal cell death, and suppresses oxidative stress in brain tissue. The compound's antioxidant properties diminish oxidative stress, reduce reactive oxygen species production, decrease neurotoxicity, and combat neuroinflammation. However, most brain health evidence comes from cell and animal studies. Human clinical trials specifically examining cognitive outcomes are needed.
Can fisetin help with aging?
Fisetin shows promising anti-aging effects in animal research. The landmark senolytic study found fisetin extended both median and maximum lifespan in aged mice and reduced age-related pathology. Intermittent fisetin supplementation improved physical function and decreased cellular senescence markers in skeletal muscle with aging, with improvements comparable to genetic senescent cell clearance. Human evidence is more limited. A pilot study showed variable individual responses: 4/10 participants reduced biological aging, 5/10 increased, and 1/10 showed no change.
Should I take fisetin with food?
Taking fisetin with food, particularly meals containing healthy fats, is generally recommended to potentially improve absorption. Fisetin has poor water solubility and limited bioavailability in its standard form. Nanodelivery methods and structure modifications have been developed to improve bioavailability. A clinical study of an enhanced hydrogel formulation demonstrated significantly improved absorption compared to unformulated fisetin. Consider enhanced formulations if bioavailability is a concern.
Does fisetin interact with medications?
Yes, fisetin has documented enzyme interactions. Research demonstrates fisetin selectively inhibits CYP2C8 in human liver microsomes with an equilibrium dissociation constant of 4.1 μM. Its metabolite geraldol also inhibits the same enzyme at 11.5 μM. CYP2C8 metabolizes several medications including repaglinide (diabetes), paclitaxel (chemotherapy), and amodiaquine (antimalarial). If you take medications metabolized by this enzyme, consult your healthcare provider before using fisetin. Inform your doctor of all supplements you take.
Is fisetin safe for pregnant women?
Human safety data for fisetin during pregnancy is not available. Animal research examined gestational fisetin intake at 10-50 mg/kg doses, finding the lower dose (10 mg/kg) more effective for protecting developing offspring from mercury-induced neurotoxicity. The study noted fisetin decreased oxidative stress markers and protected brain regions from morphological damage in rat offspring. However, animal results do not directly translate to human safety. Pregnant women should consult their healthcare provider before taking fisetin or any supplement not specifically indicated for pregnancy.
Our Accuracy Commitment and Editorial Principles
At Biochron, we take health information seriously. Every claim in this article is supported by peer-reviewed scientific evidence from reputable sources published in 2015 or later. We use a rigorous evidence-grading system to help you understand the strength of research behind each statement:
- [Evidence: A] = Systematic review or meta-analysis (strongest evidence)
- [Evidence: B] = Randomized controlled trial (RCT)
- [Evidence: C] = Cohort or case-control study
- [Evidence: D] = Expert opinion or clinical guideline
Our editorial team follows strict guidelines: we never exaggerate health claims, we clearly distinguish between correlation and causation, we update content regularly as new research emerges, and we transparently note when evidence is limited or conflicting. For our complete editorial standards, visit our Editorial Principles page.
This article is for informational purposes only and does not constitute medical advice. Always consult qualified healthcare professionals before making changes to your health regimen, especially if you have medical conditions or take medications.
References
- 1 . Fisetin is a senotherapeutic that extends health and lifespan, Yousefzadeh MJ et al., EBioMedicine, 2018, 36:18-28, PubMed | DOI [Evidence: A]
- 2 . Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: Study protocol, Silva M et al., Trials, 2024, 25(1):698, PubMed | DOI [Evidence: B]
- 3 . Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era, Verdoorn BP et al., J Am Geriatr Soc, 2021, 69(11):3023-3033, PubMed | DOI [Evidence: B]
- 4 . The Effects of Fisetin on Reducing Biological Aging: A Pilot Study, Lee E, Burns M, Altern Ther Health Med, 2024, 30(9):6-10, PubMed [Evidence: B]
- 5 . Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks, Lee E et al., Aging, 2024, 16(4):3088-3106, PubMed | DOI [Evidence: B]
- 6 . Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence, Murray KO et al., Aging Cell, 2025, 24(8):e70114, PubMed | DOI [Evidence: B]
- 7 . The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases, Hassan SSU et al., Front Pharmacol, 2022, 13:1015835, PubMed | DOI [Evidence: C]
- 8 . Fisetin-In Search of Better Bioavailability-From Macro to Nano Modifications: A Review, Szymczak J, Cielecka-Piontek J, Int J Mol Sci, 2023, 24(18):14158, PubMed | DOI [Evidence: C]
- 9 . Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin, Krishnakumar IM et al., J Nutr Sci, 2022, 11:e74, PubMed | DOI [Evidence: B]
- 10 . Selective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, Shrestha R et al., Drug Metab Pharmacokinet, 2018, 33(2):111-117, PubMed | DOI [Evidence: C]
- 11 . Neuroprotective Effects of Fisetin in Alzheimer's and Parkinson's Diseases, Nabavi SF et al., Curr Top Med Chem, 2016, 16(17):1910-5, PubMed | DOI [Evidence: C]
- 12 . Fisetin Prolongs Therapy Window of Brain Ischemic Stroke Using Tissue Plasminogen Activator, Wang L et al., Clin Appl Thromb Hemost, 2019, 25:1076029619871359, PubMed | DOI [Evidence: B]
- 13 . Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential, Mirza MA et al., Curr Pharm Biotechnol, 2025, 26(8):1143-1158, PubMed | DOI [Evidence: D]
- 14 . Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients, Farsad-Naeimi A et al., Food Funct, 2018, 9(4):2025-2031, PubMed | DOI [Evidence: B]
- 15 . Fisetin induces apoptosis in colorectal cancer cells by suppressing autophagy, Pandey A, Trigun SK, J Cell Biochem, 2023, 124(9):1289-1308, PubMed | DOI [Evidence: B]
- 16 . Fisetin: An anticancer perspective, Imran M et al., Food Sci Nutr, 2020, 9(1):3-16, PubMed | DOI [Evidence: D]
- 17 . Fisetin Alleviates Inflammation and Oxidative Stress in Deep Vein Thrombosis via MAPK and NRF2, Liu H, Lu Q, Int J Mol Sci, 2024, 25(7):3724, PubMed | DOI [Evidence: C]
- 18 . Effect of Gestational Intake of Fisetin on Developmental Methyl Mercury Neurotoxicity, Jacob S, Thangarajan S, Biol Trace Elem Res, 2017, 177(2):297-315, PubMed | DOI [Evidence: C]
- 19 . Fisetin as a chemoprotective and chemotherapeutic agent, Fatima R et al., Med Oncol, 2025, 42(4):104, PubMed | DOI [Evidence: D]
Medical Disclaimer
This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers are advised to consult their doctors or qualified health professionals regarding specific health questions and before making any changes to their health routine, including starting new supplements.
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