What is Fisetin?
Fisetin is a naturally occurring plant polyphenol belonging to the flavonol subgroup of flavonoids. It was first identified in 1891 and is found in many fruits and vegetables, most notably strawberries. Unlike many other flavonoids, fisetin has recently attracted considerable scientific interest due to its potent senolytic properties—meaning it can selectively clear out senescent cells from the body, which accumulate with age and contribute to age-related diseases and systemic inflammation.
Senescent cells enter a state where they stop dividing but do not die. Instead, they secrete harmful substances collectively known as the senescence-associated secretory phenotype (SASP), which includes inflammatory cytokines, enzymes, and growth factors that damage surrounding tissues. Fisetin has shown remarkable ability in preclinical studies to target and eliminate these cells, particularly in aged mice, where it not only improved health markers but also extended lifespan by over 30%.
How Fisetin Works in the Body
Fisetin works via multiple biological pathways. First and foremost, it induces apoptosis (programmed cell death) in senescent cells by activating certain pro-apoptotic genes and inhibiting anti-apoptotic ones. This is a key mechanism behind its senolytic effect. Additionally, fisetin acts as a powerful antioxidant, neutralizing free radicals and upregulating endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase. This contributes to reducing oxidative stress, which is a major factor in aging and neurodegeneration.
On the neurological front, fisetin crosses the blood-brain barrier and has been shown to enhance memory, learning, and synaptic plasticity in animal models. It promotes neuronal differentiation and protects against glutamate-induced excitotoxicity—a harmful process implicated in diseases like Alzheimer’s. It also modulates important signaling pathways such as PI3K/Akt, Nrf2, and mTOR, which are crucial in cell survival, stress resistance, and metabolism.
Clinical Evidence and Studies
While much of the robust data comes from animal models, there are ongoing human clinical trials that are beginning to validate fisetin’s benefits. A notable example is the AFFIRM trial (at the Mayo Clinic), which investigates the effects of high-dose fisetin on age-related frailty. Initial findings have been promising, with markers of inflammation and senescence significantly reduced following short-term supplementation.
Other studies are examining fisetin’s potential in treating cognitive impairment, chronic kidney disease, and even COVID-19 complications, due to its anti-inflammatory effects. However, large-scale placebo-controlled studies are still needed before fisetin can be formally recommended as a therapeutic drug. That said, its over-the-counter availability as a supplement has made it popular among longevity and biohacking communities.
How to Take Fisetin
Fisetin can be taken in two main ways:
Daily low-dose supplementation for general antioxidant and neuroprotective benefits.
High-dose intermittent protocol for senolytic purposes (e.g., clearing senescent cells).
The senolytic approach is currently the most well-studied. In this method, individuals take 20 mg/kg of body weight for two consecutive days per month. This mimics the dosing used in successful rodent studies and is thought to deliver a potent pulse strong enough to eliminate senescent cells while minimizing strain on the body. For a person weighing 70 kg (~154 lbs), this translates to around 1,400 mg/day for 2 days, once a month.
Daily users typically consume between 100 to 500 mg/day. It is best absorbed when taken with food containing fat, due to its lipophilic nature. Some users enhance bioavailability by pairing it with phospholipids (liposomal fisetin) or black pepper extract (piperine), although fisetin doesn’t suffer from poor absorption to the same extent as, say, curcumin.
Supplement Forms and Quality
Fisetin is available in various forms, including capsules, tablets, powders, and liposomal liquids. The most common source is Rhus succedanea (Japanese wax tree), which is rich in fisetin extract. High-purity fisetin is typically ≥98%, and this level of purity is crucial for avoiding potentially harmful plant byproducts. Some supplements also include quercetin, another flavonoid that has mild senolytic effects and may work synergistically.
When selecting a supplement, it’s critical to choose one that has been third-party tested for purity and contaminants. Well-known brands like Life Extension, Double Wood Supplements, and ProHealth Longevity offer high-quality fisetin. Some suppliers like Science.bio provide fisetin in powder form for research use, often at a lower cost per gram, but this comes with the responsibility of accurate self-dosing and quality verification.
Safety, Side Effects, and Interactions
Fisetin is generally regarded as safe and well-tolerated. Animal studies have found no evidence of toxicity even at high doses. Human reports of side effects are rare but may include mild gastrointestinal discomfort, fatigue, or headaches, particularly with high doses. Importantly, fisetin has anticoagulant properties, which means it might increase the effects of blood thinners like warfarin or aspirin.
Fisetin also interacts with cytochrome P450 enzymes (particularly CYP3A4 and CYP2C9), which are involved in drug metabolism. Therefore, anyone on medications metabolized through these pathways should consult a healthcare provider before starting fisetin.
Pregnant or breastfeeding women should avoid fisetin due to lack of safety data. Similarly, people with serious liver or kidney issues should exercise caution, as the body clears flavonoids via these organs.
Ideal Stack Combinations
Fisetin’s versatility means it can be stacked with other supplements for synergistic effects. For example, combining it with NMN or NR (NAD+ boosters) may support energy metabolism and DNA repair, enhancing overall longevity. Pairing it with Lion’s Mane mushroom or citicoline can enhance its cognitive effects, especially in older adults. For senolytic cycling, some protocols use fisetin alongside quercetin or dasatinib (a prescription drug used off-label under medical supervision).
Fisetin may also complement anti-inflammatory stacks
including curcumin, resveratrol, omega-3s, and astaxanthin, all of which target
different inflammatory pathways.
Long-Term Use vs. Short-Term Pulses
There is still debate in the longevity community over whether fisetin is best used as a long-term daily supplement or in intermittent senolytic cycles. The latter is supported by the idea that senescent cells accumulate gradually, and that periodic clearance is sufficient—and perhaps safer—than continuous exposure to high-dose flavonoids. Those who prioritize senolytic benefits often opt for the 2-day/month protocol, while others aiming for general brain and antioxidant support take lower daily doses.
A hybrid approach is also used by some biohackers: low daily dose (100–200 mg) most days, with a high-dose pulse once a month. Until more human data emerges, both methods remain viable depending on your goals.
Final Thoughts
Fisetin is a fascinating compound that bridges the gap between nutrition and therapeutics. With robust evidence for clearing senescent cells, protecting the brain, and reducing inflammation, it holds tremendous promise in promoting a longer and healthier life. While more clinical trials are needed to fully validate its efficacy in humans, the early evidence is strong enough that many in the health optimization space have already incorporated it into their protocols.
Whether you’re exploring fisetin for cognitive support, anti-aging, or senolytic therapy, it’s essential to understand the correct dosage, form, timing, and safety considerations to get the most from this natural molecule. As research continues to unfold, fisetin may well become a cornerstone of future longevity medicine.
Chemical Identity
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Molecular formula: C₁₅H₁₀O₆
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Other names: 3,3′,4′,7-Tetrahydroxyflavone
๐ Natural Sources of Fisetin
| Food Source | Fisetin Content (ฮผg/g) |
|---|---|
| Strawberries | ~160 |
| Apples | ~27 |
| Persimmons | ~10.6 |
| Onions | ~4.8 |
| Grapes | ~3.9 |
| Cucumbers | ~0.1 |
Note: You would need to eat several pounds of strawberries to reach the dose used in most studies — hence the interest in supplements.
๐ง Key Benefits and Research Findings
1. Senolytic Activity
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Removes senescent (zombie) cells, which are aged, non-dividing cells that cause inflammation and aging.
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One of the most potent natural senolytics known.
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Animal studies show fisetin extends lifespan and improves healthspan.
2. Neuroprotective
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Reduces brain inflammation.
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Protects neurons and improves cognitive function.
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Shown to prevent or reduce symptoms in models of Alzheimer’s and Parkinson’s disease.
3. Antioxidant
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Strong free radical scavenger.
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Increases glutathione and other protective enzymes.
4. Anti-inflammatory
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Downregulates NF-ฮบB and pro-inflammatory cytokines (e.g., TNF-ฮฑ, IL-6).
5. Anti-cancer
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Promotes apoptosis in cancer cells.
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Inhibits tumor growth in preclinical studies (not yet confirmed in humans).
6. Metabolic Health
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May improve insulin sensitivity.
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Reduces blood sugar and cholesterol in some models.
๐ How to Take Fisetin
๐งช Common Dosage
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Typical human supplement doses: 100 mg – 500 mg/day
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Research doses (senolytic): ~20 mg/kg body weight over a few days
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For a 70 kg person: ~1,400 mg/day, taken for 2 consecutive days per month
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Based on Mayo Clinic & Scripps Institute senolytic protocol
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๐ Timing
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Senolytic use: Take a high dose for 2 days per month
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Allows clearance of senescent cells without ongoing stress
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General antioxidant/brain health: Lower daily doses (e.g., 100–200 mg/day) can be taken continuously
๐ฝ️ With or Without Food?
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Take with fat for better absorption (fisetin is fat-soluble)
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e.g., with olive oil, fish oil, or a meal containing fats
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๐ซ Cycling
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High-dose fisetin is usually cycled to avoid overburdening the liver and kidneys
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Avoid continuous high-dose unless under clinical supervision
๐ฆ Supplement Forms
๐ Capsule & Tablet
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Most common, ranging from 100 to 500 mg per capsule
๐งช Powder
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Pure fisetin powder available for custom dosing
๐งฌ Enhanced Bioavailability Forms
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Liposomal Fisetin (encased in fat bubbles for better absorption)
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Micronized/Nano Fisetin (smaller particles = better absorption)
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With Quercetin or Piperine: Sometimes combined for synergistic effects
๐ท️ Reputable Brands
Look for third-party tested and purity-certified supplements. Some trusted fisetin supplement brands:
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Life Extension
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Double Wood Supplements
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ProHealth Longevity
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RevGenetics
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Science.bio (for research purposes, purity tested)
Make sure the source is:
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≥98% pure fisetin
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Free from fillers, heavy metals, solvents
⚠️ Safety and Side Effects
✔️ Generally Recognized as Safe (GRAS)
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No major toxicity in animal or early human studies
๐ซ Potential Side Effects (at high doses)
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Gastrointestinal discomfort
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Headache or fatigue
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Possible drug interactions (especially with medications metabolized by CYP450 enzymes)
⚠️ Who Should Avoid or Be Cautious?
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Pregnant or breastfeeding women
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People with liver/kidney conditions
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Those on multiple medications — check with a healthcare provider
๐งช Clinical Trials & Human Research
There are ongoing and completed clinical trials on fisetin:
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Mayo Clinic: Investigating senolytic effects in aging
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Scripps Research Institute: Studying Alzheimer's and frailty
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Still in early phases — human data is promising but limited
๐ง Fisetin vs Other Flavonoids
| Flavonoid | Senolytic? | Neuroprotective? | Antioxidant Strength |
|---|---|---|---|
| Fisetin | ✅ Yes | ✅ Yes | ⭐⭐⭐⭐⭐ |
| Quercetin | ✅ Yes | ✅ Moderate | ⭐⭐⭐⭐ |
| Resveratrol | ❌ Not strongly | ✅ Yes | ⭐⭐⭐⭐ |
| Curcumin | ❌ | ✅ Yes | ⭐⭐⭐ |
Fisetin stands out for its unique senolytic and brain-boosting combo.
๐งฌ Stack Ideas
If you're using fisetin as part of an anti-aging or cognitive stack, here are potential synergistic combos:
| Stack Target | Add Fisetin With... |
|---|---|
| Senolytic | Quercetin, Dasatinib (under clinical use only) |
| Brain Health | Lion’s Mane, Citicoline, Bacopa |
| Longevity | NMN or NR, Resveratrol, Metformin* |
| Inflammation | Curcumin, Omega-3s, Boswellia |
*Metformin should be used only under doctor supervision.
๐งญ Summary
| Aspect | Details |
|---|---|
| What is it? | A flavonoid from fruits, with anti-aging & neuroprotective power |
| Best use | Senolytic (clearing senescent cells) |
| Dosage | 100–500 mg daily; ~20 mg/kg x 2 days/month (senolytic) |
| With food? | Yes, especially fat-containing meals |
| Key benefits | Anti-aging, antioxidant, brain function, inflammation |
| Best brands | Life Extension, Double Wood, ProHealth |
| Side effects? | Mild at low doses; high doses require care |
