Comparison
MOTS-c vs Omega-3 (EPA/DHA)
Side-by-side of MOTS-c and Omega-3 (EPA/DHA). 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.
Omega-3 (EPA/DHA)
Omega 3 fish oil profile: EPA/DHA marine fatty acids, 2-4 g/day cuts triglycerides 20-30%, REDUCE-IT showed 25% cardiovascular risk reduction on icosapent eth.
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
Omega-3 (EPA/DHA)
- •Reduces fasting triglycerides 20-50% at 2-4 g/day in hypertriglyceridemic patients
- •REDUCE-IT showed 25% relative risk reduction in major CV events at 4 g/day icosapent ethyl
- •Modest antidepressant effect (SMD ~0.40) for EPA-dominant formulations at 1-2 g/day
- •Atrial fibrillation incidence rises ~30-50% at 4 g/day; relevant for older patients with pre-existing CV disease
- •Tissue omega-3 index (RBC EPA + DHA) target ~8%; Western baseline typically 4-5%
- •Triglyceride and re-esterified triglyceride forms absorb ~70% better than ethyl esters in fasted state
Side-by-side
| Attribute | MOTS-c | Omega-3 (EPA/DHA) |
|---|---|---|
| Category | peptide | supplement |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | fish oil, EPA, DHA, marine omega-3 |
| Half-life (hr) ↗ | 0.5 | 48 |
| Typical dose (mg) ↗ | 5 | 2000 |
| Dosing frequency | 2-3x weekly | 1 to 2 times daily with food |
| Routes | subcutaneous | oral |
| Onset (hr) | 1 | 4 |
| Peak (hr) | 4 | 12 |
| Molecular weight | 1880.18 | 302.45 |
| Molecular formula | C82H132N22O25S2 | C20H30O2 (EPA); C22H32O2 (DHA) |
| 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. | Substitutes arachidonic acid in membrane phospholipids, shifting eicosanoid production toward less-inflammatory 3-series prostaglandins and 5-series leukotrienes. Activates PPAR-alpha to lower hepatic VLDL/triglyceride synthesis. DHA modulates synaptic membrane fluidity and neuronal function. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | Dietary supplement; prescription forms (icosapent ethyl, omega-3 acid ethyl esters) for severe hypertriglyceridemia |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | Not scheduled |
| Pregnancy | Insufficient data; not recommended | Recommended at 200 to 600 mg DHA/day for fetal development |
| CAS | 1627580-64-6 | 10417-94-4 |
| PubChem CID | 139599184 | 446284 |
| Wikidata | Q24832108 | Q207688 |
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)
Omega-3 (EPA/DHA)
Common side effects
- fishy aftertaste
- eructation (fish burps)
- mild dyspepsia
- loose stools at high doses
Contraindications
- fish allergy (use algal omega-3 alternative)
- active bleeding disorders
- scheduled surgery (discontinue 5-7 days prior)
Interactions
- warfarin and DOACs: additive antiplatelet effect at 2+ g/day; meaningful bleeding risk(moderate)
- aspirin and antiplatelet agents: additive bleeding risk at high doses(moderate)
- statins: complementary cardiovascular effects; no pharmacokinetic interaction(minor)
- antiarrhythmics: high-dose omega-3 increases AF risk; relevant in pre-existing arrhythmia(moderate)
Which Should You Take?
Omega-3 (EPA/DHA) 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 cardiovascular health, pick Omega-3 (EPA/DHA).
- → If your priority is focus or working memory, pick Omega-3 (EPA/DHA).
Edge case: If you want to avoid research-only / gray-market sourcing, Omega-3 (EPA/DHA) is the more accessible choice.
Default choice: Omega-3 (EPA/DHA). 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 Omega-3 (EPA/DHA)?
MOTS-c and Omega-3 (EPA/DHA) 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 Omega-3 (EPA/DHA)?
MOTS-c half-life is 0.5 hours; Omega-3 (EPA/DHA) half-life is 48 hours.
Can you stack MOTS-c with Omega-3 (EPA/DHA)?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper