Comparison
MOTS-c vs NMN
Side-by-side of MOTS-c and NMN. 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.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
NMN
NMN supplements are oral nicotinamide mononucleotide capsules sold for longevity, energy, and metabolic health. They raise plasma NAD+ 30-90% at 250-1000.
Effects at a glance
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
NMN
- •Plasma NAD+ rises 30-90% at 250-1000 mg/day across human PK studies
- •Tissue NAD+ rise is inconsistent across human trials (Yoshino 2021, Igarashi 2022)
- •No human trials measure hard endpoints (mortality, CV events, cancer); evidence is biomarker-only
- •Most trials cluster at 250-500 mg/day; dose-response above 250 mg/day is poorly characterized
- •FDA position contested; widely sold as supplement but with regulatory uncertainty
- •Marketing claims for fertility and longevity outrun the human trial evidence substantially
Side-by-side
| Attribute | MOTS-c | NMN |
|---|---|---|
| Category | peptide | supplement |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | nicotinamide mononucleotide, beta-NMN |
| Half-life (hr) ↗ | 0.5 | 4 |
| Typical dose (mg) ↗ | 5 | 250 |
| Dosing frequency | 2-3x weekly | 1x daily, often morning |
| Routes | subcutaneous | oral, sublingual |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 3 |
| Molecular weight | 1880.18 | 334.22 |
| Molecular formula | C82H132N22O25S2 | C11H15N2O8P |
| Mechanism | 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. | Direct precursor in the NAD+ salvage pathway; converted to NAD+ by NMNAT enzymes in essentially every tissue. Raised NAD+ supports sirtuin and PARP enzyme activity. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | Contested in US (FDA position 2022); widely sold as supplement; broadly available in EU, UK, Asia |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | Not scheduled |
| Pregnancy | Insufficient data; not recommended | Insufficient data; precautionary avoidance |
| CAS | 1627580-64-6 | 1094-61-7 |
| PubChem CID | 139599184 | 14180 |
| Wikidata | Q24832108 | Q418972 |
Safety profile
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)
NMN
Common side effects
- mild GI upset (rare)
- occasional headache
- flushing (rare)
Contraindications
- pregnancy and lactation (precautionary, no data)
- active cancer (theoretical concern, not evidence-based)
Interactions
- metformin: no clinically significant interaction documented; both modulate metabolism through different mechanisms(minor)
- chemotherapy agents: theoretical concern about supporting cancer cell proliferation; coordinate with oncology team(moderate)
- CD38 inhibitors: would amplify NMN-induced NAD+ rise; not clinically relevant for most users(minor)
Which Should You Take?
NMN comes out ahead for most readers on the criteria we weight: 3 catalogued goals, Contested in US (FDA position 2022); widely sold as supplement; broadly available in EU, UK, Asia, 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 mitochondrial function, pick MOTS-c.
- → If your priority is energy and stamina, pick NMN.
- → If your priority is healthspan extension, pick NMN.
Edge case: If you cannot self-administer injections, NMN is the only oral option in this pair.
Default choice: NMN. 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 MOTS-c and NMN?
MOTS-c and NMN differ in category (peptide vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, MOTS-c or NMN?
MOTS-c half-life is 0.5 hours; NMN half-life is 4 hours.
Can you stack MOTS-c with NMN?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper