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Fisetin
A flavonoid found in strawberries with potent senolytic, anti-inflammatory, and neuroprotective properties - shown to clear senescent cells, support long-term potentiation for memory, and protect against age-related cognitive decline.
Benefits
What is Fisetin?
Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid found in highest concentrations in strawberries, with smaller amounts in apples, persimmons, grapes, onions, and cucumbers. It has emerged as one of the most exciting compounds in the longevity and neuroprotection fields due to its dual activity as both a senolytic agent (capable of selectively destroying senescent "zombie" cells) and a direct neuroprotective compound.
Fisetin's neuroprotective credentials are substantial. A landmark 2006 study by Dr Pamela Maher's group at the Salk Institute, published in Proceedings of the National Academy of Sciences, demonstrated that fisetin promoted the differentiation of neural precursor cells and enhanced long-term potentiation (LTP) in hippocampal neurons - the cellular mechanism underlying memory formation. A 2018 study published in EBioMedicine by the Mayo Clinic found that fisetin was the most potent senolytic among 10 flavonoids tested, selectively killing senescent cells in human tissue and extending healthy lifespan in aged mice by 10%. Fisetin also activates the Nrf2 antioxidant pathway, inhibits NF-kB-driven inflammation, maintains glutathione levels, and modulates multiple kinase cascades involved in neuronal survival. This combination of acute neuroprotection, long-term senolytic activity, and memory-enhancing effects makes it a uniquely versatile compound for brain health.
- Senolytic activity: Selectively induces apoptosis in senescent cells - dysfunctional cells that accumulate with age and secrete pro-inflammatory factors (SASP) that damage surrounding tissue including neurons
- Long-term potentiation enhancement: Facilitates LTP in hippocampal neurons via ERK/CREB signalling pathway activation, directly supporting memory formation
- Nrf2 activation: Activates the Nrf2 antioxidant pathway, upregulating glutathione synthesis and endogenous antioxidant enzyme production
- NF-kB inhibition: Suppresses inflammatory signalling, reducing neuroinflammation and microglial overactivation
- GSK-3beta inhibition: Inhibits glycogen synthase kinase-3 beta, reducing tau phosphorylation (relevant to Alzheimer's pathology)
- Glutathione maintenance: Uniquely effective at maintaining intracellular glutathione levels under oxidative stress conditions
- Daily neuroprotective dosage: 100-500 mg per day
- Senolytic protocol: Some longevity researchers suggest intermittent high-dose protocols (e.g. 500-1,000 mg for 2 consecutive days per month), though human senolytic dosing is not yet established
- Bioavailability: Fisetin has low oral bioavailability. Liposomal formulations or taking with a fat source may improve absorption
- Food sources: Strawberries are the richest dietary source (approximately 160 mcg/g), but you would need to eat several kilograms daily to reach supplement doses
- Onset: Antioxidant and anti-inflammatory effects occur with daily use. Senolytic benefits are measured over months
- Generally well tolerated: Fisetin has a long history of dietary exposure through fruit consumption and limited adverse effects in studies
- Limited human trial data: While animal and in vitro data are extensive, large-scale human trials specifically for fisetin are ongoing (Mayo Clinic AFFIRM trials)
- Potential drug interactions: May inhibit CYP450 enzymes at high doses. Consult your doctor if taking medications with narrow therapeutic windows
- Anticoagulant interaction: Theoretical interaction with blood-thinning medications. Use caution and consult your doctor
- Pregnancy and breastfeeding: Insufficient data for supplement-dose fisetin. Dietary intake from fruit is safe
Natural Sources & Forms
- Capsules: Available from longevity and nootropic supplement retailers in 100-500 mg capsules
- Liposomal formulations: Enhanced bioavailability formulations using liposomal delivery
- Food sources: Strawberries (richest source), apples, persimmons, grapes, onions, mangoes, kiwi, and cucumbers
Frequently Asked Questions
A flavonoid found in strawberries with potent senolytic, anti-inflammatory, and neuroprotective properties - shown to clear senescent cells, support long-term potentiation for memory, and protect against age-related cognitive decline.
The key benefits of Fisetin include: Cognitive Enhancement, Focus, Longevity, Memory, Mood, Stress Relief.
Senolytic activity: Selectively induces apoptosis in senescent cells - dysfunctional cells that accumulate with age and secrete pro-inflammatory factors (SASP) that damage surrounding tissue including neurons Long-term potentiation enhancement: Facilitates LTP in hippocampal neurons via ERK/CREB signalling pathway activation, directly supporting memory formation Nrf2 activation: Activates the Nrf2 antioxidant pathway, upregulating glutathione synthesis and endogenous antioxidant enzyme production NF-kB inhibition: Suppresses inflammatory signalling, reducing neuroinflammation and microglial overactivation GSK-3beta inhibition: Inhibits glycogen synthase kinase-3 beta, reducing tau phosphorylation (relevant to Alzheimer's pathology) Glutathione maintenance: Uniquely effective at maintaining intracellular glutathione levels under oxidative stress conditions
Daily neuroprotective dosage: 100-500 mg per day Senolytic protocol: Some longevity researchers suggest intermittent high-dose protocols (e.g. 500-1,000 mg for 2 consecutive days per month), though human senolytic dosing is not yet established Bioavailability: Fisetin has low oral bioavailability. Liposomal formulations or taking with a fat source may improve absorption Food sources: Strawberries are the richest dietary source (approximately 160 mcg/g), but you would need to eat several kilograms daily to reach supplement doses Onset: Antioxidant and anti-inflammatory effects occur with daily use. Senolytic benefits are measured over months
Generally well tolerated: Fisetin has a long history of dietary exposure through fruit consumption and limited adverse effects in studies Limited human trial data: While animal and in vitro data are extensive, large-scale human trials specifically for fisetin are ongoing (Mayo Clinic AFFIRM trials) Potential drug interactions: May inhibit CYP450 enzymes at high doses. Consult your doctor if taking medications with narrow therapeutic windows Anticoagulant interaction: Theoretical interaction with blood-thinning medications. Use caution and consult your doctor Pregnancy and breastfeeding: Insufficient data for supplement-dose fisetin. Dietary intake from fruit is safe
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