Comparison
Fisetin vs MOTS-c
Side-by-side of Fisetin and MOTS-c. 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.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
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
MOTS-c
- •16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
- •Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
- •Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
- •CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
- •Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
- •Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism
Side-by-side
| Attribute | Fisetin | MOTS-c |
|---|---|---|
| Category | supplement | peptide |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 2 | 0.5 |
| Typical dose (mg) ↗ | 500 | 5 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | 2-3x weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 4 |
| Molecular weight | 286.24 | 1880.18 |
| Molecular formula | C15H10O6 | C82H132N22O25S2 |
| 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-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling. |
| Legal status | OTC dietary supplement | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | allowed | unknown |
| DEA / Rx | OTC supplement | Not scheduled (research chemical) |
| Pregnancy | Insufficient data | Insufficient data; not recommended |
| CAS | 528-48-3 | 1627580-64-6 |
| PubChem CID | 5281614 | 139599184 |
| Wikidata | Q230614 | Q24832108 |
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)
MOTS-c
Common side effects
- injection-site irritation
- transient fatigue
- headache (anecdotal)
Contraindications
- pregnancy
- lactation
- active malignancy (theoretical)
- severe hypoglycemia risk on concurrent insulin or sulfonylurea
Interactions
- insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
- metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
- sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(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. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is focus or working memory, pick Fisetin.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is mitochondrial function, pick MOTS-c.
Edge case: If you want to avoid research-only / gray-market sourcing, Fisetin is the more accessible choice.
Default choice: Fisetin. Lower friction to source, and broader goal coverage. Reach for MOTS-c 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 MOTS-c?
Fisetin and MOTS-c differ in category (supplement vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or MOTS-c?
Fisetin half-life is 2 hours; MOTS-c half-life is 0.5 hours.
Can you stack Fisetin with MOTS-c?
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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