Comparison
MOTS-c vs Nicotinamide Riboside
Side-by-side of MOTS-c and Nicotinamide Riboside. 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.
Nicotinamide Riboside
Nicotinamide riboside (NR) is the most-studied NAD+ precursor in humans. Sold as Niagen by Chromadex; raises plasma NAD+ 30-60% at 250-1,000 mg/day.
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
Nicotinamide Riboside
- •Most-studied NAD+ precursor in human trials; the original Niagen formulation by Chromadex
- •Plasma NAD+ rises 30-60% at 250-1,000 mg/day across multiple human PK trials
- •Martens 2018 reported reduced BP and arterial stiffness at 500 mg/day for 6 weeks
- •Dollerup 2018 found no insulin sensitivity change despite plasma NAD+ rise
- •Tissue NAD+ rise inconsistent; hard clinical endpoints not yet measured
- •Larger human safety database than NMN; comparable mechanistic effects
Side-by-side
| Attribute | MOTS-c | Nicotinamide Riboside |
|---|---|---|
| Category | peptide | supplement |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | NR, Niagen, nicotinamide riboside chloride |
| Half-life (hr) ↗ | 0.5 | 8 |
| Typical dose (mg) ↗ | 5 | 500 |
| Dosing frequency | 2-3x weekly | daily, typically morning |
| Routes | subcutaneous | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 4 |
| Molecular weight | 1880.18 | 255.25 |
| Molecular formula | C82H132N22O25S2 | C11H15N2O5 |
| 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. | NAD+ precursor via salvage pathway. Phosphorylated to NMN by nicotinamide riboside kinase (NRK), then converted to NAD+. Substrate for sirtuins, PARPs, and CD38. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | OTC dietary supplement |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | OTC supplement |
| Pregnancy | Insufficient data; not recommended | Insufficient data at supplement doses |
| CAS | 1627580-64-6 | 1341-23-7 |
| PubChem CID | 139599184 | 439924 |
| Wikidata | Q24832108 | Q3343054 |
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)
Nicotinamide Riboside
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- pregnancy / lactation (insufficient data)
- active cancer (theoretical, no contraindicating data)
Interactions
- pterostilbene: complementary sirtuin pathway (Basis combination)(minor)
- TMG (trimethylglycine): methylation support during high NAD+ precursor dosing(minor)
Which Should You Take?
Nicotinamide Riboside comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, 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 Nicotinamide Riboside.
- → If your priority is healthspan extension, pick Nicotinamide Riboside.
Edge case: If you want to avoid research-only / gray-market sourcing, Nicotinamide Riboside is the more accessible choice.
Default choice: Nicotinamide Riboside. Lower friction to source, 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 Nicotinamide Riboside?
MOTS-c and Nicotinamide Riboside 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 Nicotinamide Riboside?
MOTS-c half-life is 0.5 hours; Nicotinamide Riboside half-life is 8 hours.
Can you stack MOTS-c with Nicotinamide Riboside?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper