Comparison
Fisetin vs Spermidine
Side-by-side of Fisetin and Spermidine. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Fisetin
Fisetin is a flavonoid found in strawberries with senolytic activity in mouse models. Hickson 2019 confirmed senescent-cell clearance in human adipose tissue.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
Effects at a glance
Fisetin
- •Flavonoid found in strawberries; most potent natural senolytic in screening assays (Yousefzadeh 2018)
- •Hickson 2019 confirmed reduced senescent-cell burden in human adipose tissue at 20 mg/kg pulsed for 2 days
- •Pulsed Mayo protocol (20 mg/kg/day x 2 days monthly) is the only dose with human biomarker evidence
- •Daily low-dose (100-500 mg) is mechanistically weaker but commonly used
- •Low oral bioavailability; with-fat dosing modestly improves absorption
- •Active cancer is a relative contraindication pending clearer polyphenol-treatment data
Spermidine
- •Endogenous polyamine that induces autophagy via EP300 acetyltransferase inhibition and TFEB activation
- •Concentrated in wheat germ, soybeans, aged cheese, and mushrooms; ~10 to 15 mg/day in Mediterranean diets
- •Eisenberg 2016 reported dietary spermidine extended mouse lifespan and improved cardiac function
- •Wirth 2018 pilot (n=28) reported cognitive signal at 0.9 mg/day in older adults at risk for dementia
- •Larger Wirth 2019 follow-up (n=85) did not replicate the memory benefit at 12 months
- •Generally regarded as safe at supplemental doses; food-source position is reassuring
Side-by-side
| Attribute | Fisetin | Spermidine |
|---|---|---|
| Category | supplement | supplement |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 2 | 6 |
| Typical dose (mg) ↗ | 500 | 1.2 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | daily, typically morning with food |
| Routes | oral | oral |
| Onset (hr) | 1 | 2 |
| Peak (hr) | 4 | 4 |
| Molecular weight | 286.24 | 145.25 |
| Molecular formula | C15H10O6 | C7H19N3 |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | Induces macroautophagy via inhibition of EP300 histone acetyltransferase and activation of TFEB-mediated lysosomal biogenesis. Substrate for hypusination of eIF5A, required for translation of mitochondrial respiration proteins. |
| Legal status | OTC dietary supplement | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement | OTC supplement (not scheduled) |
| Pregnancy | Insufficient data | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 528-48-3 | 124-20-9 |
| PubChem CID | 5281614 | 1102 |
| Wikidata | Q230614 | Q411089 |
Safety profile
Fisetin
Common side effects
- mild GI upset
- headache (rare)
Contraindications
- active cancer (theoretical, polyphenol interactions)
- pregnancy and lactation (insufficient data)
- concurrent CYP3A4-sensitive medications
Interactions
- statins (CYP3A4 substrates): theoretical reduction in statin clearance at high fisetin doses(minor)
- warfarin: theoretical CYP-mediated interaction; monitor INR if combining(moderate)
- other senolytics (rapamycin, dasatinib + quercetin): additive senolytic effect; pairing is investigational(minor)
Spermidine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- wheat-germ allergy or celiac disease (for wheat-germ-extract products)
- active cancer (theoretical)
- pregnancy and lactation (insufficient data)
Interactions
- DFMO (difluoromethylornithine): competing polyamine metabolism; do not combine without oncology guidance(moderate)
Which Should You Take?
Spermidine comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. Fisetin is the right call when one of the conditionals below applies.
- → If your priority is healthspan extension, pick Spermidine.
- → If your priority is focus or working memory, pick Spermidine.
Edge case: Half-lives differ materially (Fisetin ~2 hr vs Spermidine ~6 hr). Spermidine reaches steady state faster; Fisetin is easier to dial in if tolerability is uncertain.
Default choice: Spermidine. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Fisetin only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Fisetin and Spermidine?
Fisetin and Spermidine differ in category (supplement vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or Spermidine?
Fisetin half-life is 2 hours; Spermidine half-life is 6 hours.
Can you stack Fisetin with Spermidine?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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