Comparison
Methylene Blue vs MOTS-c
Side-by-side of Methylene Blue 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.
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.
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
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
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 | Methylene Blue | MOTS-c |
|---|---|---|
| Category | pharmaceutical | peptide |
| Also known as | Methylthioninium chloride, Provayblue, tetramethylthionine chloride | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 5.5 | 0.5 |
| Typical dose (mg) ↗ | 70 | 5 |
| Dosing frequency | 1 to 3 times daily for cognitive use; single IV dose for methemoglobinemia | 2-3x weekly |
| Routes | oral, intravenous | subcutaneous |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1.5 | 4 |
| Molecular weight | 319.85 | 1880.18 |
| Molecular formula | C16H18ClN3S | C82H132N22O25S2 |
| Mechanism | 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. | 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 | Prescription (injectable, FDA approved); supplement form (oral) widely available; not scheduled | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | allowed | unknown |
| DEA / Rx | Not scheduled in the US | Not scheduled (research chemical) |
| Pregnancy | Contraindicated | Insufficient data; not recommended |
| CAS | 61-73-4 | 1627580-64-6 |
| PubChem CID | 6099 | 139599184 |
| Wikidata | Q409021 | Q24832108 |
Safety profile
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)
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?
Methylene Blue comes out ahead for most readers on the criteria we weight: 3 catalogued goals, controlled substance, oral dosing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is focus or working memory, pick Methylene Blue.
- → If your priority is mitochondrial function, pick Methylene Blue.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
Edge case: If you cannot self-administer injections, Methylene Blue is the only oral option in this pair.
Default choice: Methylene Blue. Wider use case, a Tier-A evidence outcome catalogued, 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 Methylene Blue and MOTS-c?
Methylene Blue and MOTS-c differ in category (pharmaceutical vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Methylene Blue or MOTS-c?
Methylene Blue half-life is 5.5 hours; MOTS-c half-life is 0.5 hours.
Can you stack Methylene Blue 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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