A quiet analytical research laboratory at night, racks of glass vials along a dim bench.

MOTS-c

MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA that regulates metabolism in mice. It has no approved human use, human evidence is limited to observational measurements and early analog work, and it falls under WADA S0. Vegalab does not make, sell or source MOTS-c.

What MOTS-c is

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c, about 2.2 kDa) was described in 2015. In mice it acts on skeletal muscle through the folate cycle and AMPK activation, improving insulin sensitivity and preventing diet-induced obesity. Under metabolic stress it can translocate to the nucleus and influence gene expression. Circulating levels in humans change with exercise and age in observational studies. Research on mitochondrial-derived peptides, including humanin, is an active academic field.

Regulatory status

MOTS-c is not approved anywhere and cannot be sold as a supplement. An analog, CB4211, entered early clinical testing for fatty liver disease and obesity. FDA placed MOTS-c in the 503A Category 2 list and in April 2026 announced its removal pending review, which concerns compounding only. As a non-approved substance with metabolic effects, it falls under WADA S0, and WADA-accredited laboratories have developed detection methods. Buyers should note that products labeled MOTS-c are unregulated.

The delivery problem

Like other unmodified linear peptides of this size, MOTS-c is protease-sensitive, has a short half-life and negligible oral bioavailability. Mouse studies used intraperitoneal injection. There are no published human pharmacokinetic data for the native peptide. Peptide products sold online as MOTS-c have not been characterized in published studies, so identity, purity and sterility are unknown. Any serious development program would first need validated assays for the peptide in plasma, stability data in biological fluids, and animal pharmacokinetics by the intended route.

Why this page exists

MOTS-c is part of the mitochondrial-derived peptide research field and is widely marketed online. This page states the evidence tier: mouse data, no approved use, no human efficacy trials of the native peptide. The field is early. Observational links between circulating MOTS-c and exercise or age do not show that giving the peptide produces benefits in people. This page exists to set out that evidence tier clearly for clinicians, researchers and partners, and to separate delivery science from product marketing.

Key facts

MOTS-c regulates insulin sensitivity and metabolic homeostasis in mice through skeletal muscle and AMPK activation (Lee et al. 2015, Cell Metab 21:443)
Exercise induces MOTS-c expression in human skeletal muscle and plasma (Reynolds et al. 2021, Nat Commun 12:470)
FDA announced in April 2026 that MOTS-c would be removed from Category 2 of the 503A bulks list pending further evaluation (FDA 503A bulk drug substances update, April 2026)
Non-approved substances are prohibited at all times under S0 (WADA Prohibited List 2026)

How our delivery technology applies

MOTS-c is a research model, not a product. It represents the typical short, unmodified peptide: rapid proteolysis and clearance. Multi-layer encapsulation can provide protease shielding and sustained release to extend exposure after a single administration, and those properties can be measured in plasma stability and animal PK studies with a partner who holds a legitimate research or development pathway.

Researchers: discuss protease-shielded peptide formats with Vegalab.