Comparison
Fisetin vs Lion's Mane
Side-by-side of Fisetin and Lion's Mane. 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.
Lion's Mane
Lion's mane mushroom (Hericium erinaceus) supplement profile: hericenones and erinacines stimulate NGF in vitro. Human cognition trials are small.
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
Lion's Mane
- •Edible medicinal mushroom containing NGF-stimulating hericenones and erinacines
- •Mori 2009 trial (n=30) in mild cognitive impairment showed cognitive improvement at 3 g/day for 16 weeks, reversing 4 weeks after discontinuation
- •Saitsu 2019 (n=31) in older adults reported MoCA improvements at 3.2 g/day over 12 weeks
- •Multiple small mood trials suggest reduced anxiety and depression scores at 1 to 4 g/day extract
- •Mechanistic case rests on NGF stimulation and remyelination support; in vivo human NGF measurement is absent
- •Product quality varies substantially; mycelium-on-grain products can be over 50% grain by weight
Side-by-side
| Attribute | Fisetin | Lion's Mane |
|---|---|---|
| Category | supplement | natural |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | Hericium erinaceus, Yamabushitake, Bearded Tooth, Hou Tou Gu |
| Half-life (hr) ↗ | 2 | 6 |
| Typical dose (mg) ↗ | 500 | 1000 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | 1 to 2 times daily |
| Routes | oral | oral |
| Onset (hr) | 1 | 168 |
| Peak (hr) | 4 | 1344 |
| Molecular weight | 286.24 | - |
| Molecular formula | C15H10O6 | mixed extract |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | Hericenones and erinacines stimulate NGF mRNA expression and NGF protein release in cultured neurons; secondary anti-inflammatory and remyelination-supportive activity in preclinical models. |
| Legal status | OTC dietary supplement | Dietary supplement and food worldwide; unscheduled and unrestricted |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement | OTC supplement and food |
| Pregnancy | Insufficient data | Insufficient data for routine supplementation; consumed historically as food without documented harm |
| CAS | 528-48-3 | |
| PubChem CID | 5281614 | |
| Wikidata | Q230614 | Q146050 |
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)
Lion's Mane
Common side effects
- mild GI upset
- occasional skin rash
- contact dermatitis (rare)
Contraindications
- mushroom allergy
Interactions
- anticoagulants: theoretical antiplatelet effect, no documented clinical events(minor)
Which Should You Take?
Lion's Mane comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. Fisetin is the right call when one of the conditionals below applies.
- → If your priority is healthspan extension, pick Fisetin.
- → If your priority is nerve health, pick Lion's Mane.
- → If your priority is mood, pick Lion's Mane.
Edge case: Half-lives differ materially (Fisetin ~2 hr vs Lion's Mane ~6 hr). Lion's Mane reaches steady state faster; Fisetin is easier to dial in if tolerability is uncertain.
Default choice: Lion's Mane. Lower friction to source, 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 Lion's Mane?
Fisetin and Lion's Mane differ in category (supplement vs natural), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or Lion's Mane?
Fisetin half-life is 2 hours; Lion's Mane half-life is 6 hours.
Can you stack Fisetin with Lion's Mane?
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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