Comparison
MOTS-c vs Urolithin A
Side-by-side of MOTS-c and Urolithin A. 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.
Urolithin A
Urolithin A supplement guide: pomegranate-derived metabolite, 500-1000 mg Mitopure dosing, mitophagy and muscle endurance evidence.
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
Urolithin A
- •Gut-microbiome-derived metabolite of pomegranate and walnut ellagitannins
- •Roughly 40% of adults are 'urolithin producers' from dietary intake; ~60% are non-producers
- •Ryu 2016 (Nature Medicine) reported lifespan extension in C. elegans and muscle benefits in aged rodents
- •Andreux 2019 first-in-human trial (n=60) established safety and mitochondrial gene-expression upregulation
- •Singh 2022 (n=66, 4 months, 1000 mg/day) reported improved muscle endurance in older adults
- •Most human trial portfolio is Amazentis-funded; independent replication is thin
Side-by-side
| Attribute | MOTS-c | Urolithin A |
|---|---|---|
| Category | peptide | supplement |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | UA, Mitopure, ellagitannin metabolite |
| Half-life (hr) ↗ | 0.5 | 17 |
| Typical dose (mg) ↗ | 5 | 500 |
| Dosing frequency | 2-3x weekly | daily, morning with food |
| Routes | subcutaneous | oral |
| Onset (hr) | 1 | 2 |
| Peak (hr) | 4 | 4 |
| Molecular weight | 1880.18 | 228.2 |
| Molecular formula | C82H132N22O25S2 | C13H8O4 |
| 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. | Induces mitophagy via potentiation of PINK1/Parkin signaling, leading to selective degradation of damaged mitochondria. Secondary anti-inflammatory effects via NF-kB modulation. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | OTC dietary supplement (US GRAS 2018; EFSA Novel Food 2021) |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | OTC supplement (not scheduled) |
| Pregnancy | Insufficient data; not recommended | Insufficient data; not routinely recommended |
| CAS | 1627580-64-6 | 1143-70-0 |
| PubChem CID | 139599184 | 5488186 |
| Wikidata | Q24832108 | Q27101321 |
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)
Urolithin A
Common side effects
- mild GI upset (rare)
- soft stools (rare)
Contraindications
- pregnancy and lactation (insufficient data)
- active chemotherapy (consult oncology)
Interactions
- chemotherapy agents: theoretical interaction with mitochondrial-targeting agents; consult oncologist(moderate)
Which Should You Take?
Urolithin A 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 metabolic health and glucose control, pick MOTS-c.
- → If your priority is mitochondrial function, pick MOTS-c.
- → If your priority is muscle hypertrophy, pick Urolithin A.
- → If your priority is mitochondrial function, pick Urolithin A.
Edge case: If you want to avoid research-only / gray-market sourcing, Urolithin A is the more accessible choice.
Default choice: Urolithin A. 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 Urolithin A?
MOTS-c and Urolithin A 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 Urolithin A?
MOTS-c half-life is 0.5 hours; Urolithin A half-life is 17 hours.
Can you stack MOTS-c with Urolithin A?
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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