Comparison
Fisetin vs Methylene Blue
Side-by-side of Fisetin and Methylene Blue. 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.
Methylene Blue
Methylene blue as a nootropic: low-dose cognitive enhancement, mitochondrial electron cycling, brain oxygen uptake, SSRI interaction risk, typical 0.5 to 4 mg.
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
Methylene Blue
- •FDA approved for methemoglobinemia and ifosfamide-induced encephalopathy
- •Mitochondrial electron-transport support at low doses (0.5 to 4 mg/kg) via cytochrome c shuttle
- •Potent MAO-A inhibitor; serotonin syndrome risk with SSRIs, SNRIs, MAOIs, fentanyl, tramadol, St John's wort
- •Causes harmless blue-green urine and sweat coloration; useful adherence marker
- •G6PD deficiency is an absolute contraindication; can trigger massive hemolysis
- •Cognitive-enhancement evidence is preliminary, mostly preclinical and small fMRI trials
Side-by-side
| Attribute | Fisetin | Methylene Blue |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | Methylthioninium chloride, Provayblue, tetramethylthionine chloride |
| Half-life (hr) ↗ | 2 | 5.5 |
| Typical dose (mg) ↗ | 500 | 70 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | 1 to 3 times daily for cognitive use; single IV dose for methemoglobinemia |
| Routes | oral | oral, intravenous |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 1.5 |
| Molecular weight | 286.24 | 319.85 |
| Molecular formula | C15H10O6 | C16H18ClN3S |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | Mitochondrial electron carrier at low doses (cytochrome c shuttle to complex IV) and methemoglobin reductase substrate at higher doses; potent MAO-A inhibitor across the dose range. |
| Legal status | OTC dietary supplement | Prescription (injectable, FDA approved); supplement form (oral) widely available; not scheduled |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement | Not scheduled in the US |
| Pregnancy | Insufficient data | Contraindicated |
| CAS | 528-48-3 | 61-73-4 |
| PubChem CID | 5281614 | 6099 |
| Wikidata | Q230614 | Q409021 |
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)
Methylene Blue
Common side effects
- blue-green urine and sweat
- skin and oral mucosa staining
- GI upset
- headache
- dizziness
Contraindications
- G6PD deficiency
- pregnancy
- concurrent serotonergic medication
- severe renal impairment
- infants under 6 months
Interactions
- SSRIs and SNRIs: serotonin syndrome, potentially fatal(major)
- MAOIs: additive MAO inhibition, serotonin syndrome risk(major)
- fentanyl, tramadol, meperidine: serotonin syndrome risk(major)
- dextromethorphan: serotonin syndrome risk(major)
- St John's wort: serotonin syndrome risk(major)
- lithium: additive serotonergic risk(major)
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. Methylene Blue is the right call when one of the conditionals below applies.
- → If your priority is healthspan extension, pick Fisetin.
- → If your priority is mitochondrial function, pick Methylene Blue.
- → If your priority is antimicrobial action, pick Methylene Blue.
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 Methylene Blue 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 Methylene Blue?
Fisetin and Methylene Blue 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 Methylene Blue?
Fisetin half-life is 2 hours; Methylene Blue half-life is 5.5 hours.
Can you stack Fisetin with Methylene Blue?
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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