Comparison
Fisetin vs Modafinil
Side-by-side of Fisetin and Modafinil. 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.
Modafinil
Modafinil cognitive enhancement profile: wakefulness-promoting agent, 100-200 mg dosing, 12-15 hour half-life, off-label nootropic use, Schedule IV status.
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
Modafinil
- •FDA approved in 1998 for narcolepsy, with later additions for shift-work sleep disorder and OSA residual sleepiness
- •Schedule IV controlled substance in the US; prescription-only in EU, UK, Australia
- •Increases wakefulness via weak dopamine reuptake inhibition plus histaminergic, noradrenergic, and orexinergic activation
- •Long half-life of 12 to 15 hours requires morning dosing to avoid sleep disruption
- •Modest cognitive enhancement signal in non-sleep-deprived adults at 100 to 200 mg (Battleday meta-review 2015)
- •Substantial CYP3A4 induction reduces hormonal contraceptive efficacy; barrier methods recommended
Side-by-side
| Attribute | Fisetin | Modafinil |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | Provigil, Modalert, Modvigil, diphenylmethylsulfinyl-acetamide |
| Half-life (hr) ↗ | 2 | 13 |
| Typical dose (mg) ↗ | 500 | 200 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | daily, morning |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 3 |
| Molecular weight | 286.24 | 273.35 |
| Molecular formula | C15H10O6 | C15H15NO2S |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | Weak dopamine reuptake inhibition plus downstream activation of histaminergic, noradrenergic, and orexinergic wake-promoting systems. |
| Legal status | OTC dietary supplement | Schedule IV (US); prescription-only globally; not a supplement |
| WADA status | allowed | banned |
| DEA / Rx | OTC supplement | Schedule IV |
| Pregnancy | Insufficient data | Not recommended |
| CAS | 528-48-3 | 68693-11-8 |
| PubChem CID | 5281614 | 4236 |
| Wikidata | Q230614 | Q422968 |
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)
Modafinil
Common side effects
- headache
- nausea
- anxiety
- insomnia (with late-day dosing)
- dry mouth
- mild blood pressure elevation
Contraindications
- recent myocardial infarction
- unstable angina
- left ventricular hypertrophy
- significant arrhythmia
- history of Stevens-Johnson syndrome
- psychotic disorders
- pregnancy
- concurrent MAOI use
Interactions
- hormonal contraceptives: CYP3A4 induction reduces contraceptive efficacy; use barrier method(major)
- cyclosporine: reduced cyclosporine levels via CYP3A4 induction(major)
- warfarin: CYP2C9 inhibition raises INR(moderate)
- phenytoin: CYP2C19 inhibition raises phenytoin levels(moderate)
- MAOIs: potential hypertensive reaction(major)
- classical stimulants (amphetamine, methylphenidate): additive cardiovascular and sleep-disruption effects(moderate)
Which Should You Take?
Fisetin comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. Modafinil is the right call when one of the conditionals below applies.
- → If your priority is healthspan extension, pick Fisetin.
- → If your priority is wakefulness, pick Modafinil.
- → If your priority is fatigue resistance, pick Modafinil.
Edge case: If you want to avoid controlled substance, Fisetin is the more accessible choice.
Default choice: Fisetin. Lower friction to source, and broader goal coverage. Reach for Modafinil 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 Modafinil?
Fisetin and Modafinil differ in category (supplement vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or Modafinil?
Fisetin half-life is 2 hours; Modafinil half-life is 13 hours.
Can you stack Fisetin with Modafinil?
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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