Metabolic / mitochondrial
MOTS-c
Prepared by the ezGLP team. Sources last checked . Profile reviewed .
Routes represented in the knowledgebase: Subcutaneous (SubQ).
Educational overview
MOTS-c is listed in the ezGLP knowledgebase under Metabolic / mitochondrial. Evidence and regulatory status can vary by formulation, route, and jurisdiction.
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within mitochondrial DNA rather than the nuclear genome, which places it in the small class of mitochondrial-derived peptides alongside humanin and the SHLPs. It was characterized in 2015 by a group at the University of Southern California. In cell and animal work it acts on the folate and methionine cycle, lowers cellular methionine, raises AICAR, and activates AMP-activated protein kinase (AMPK). Under metabolic stress it can move into the nucleus and alter gene expression. Circulating and muscle levels rise with exercise, which is why it is described as an exercise-mimetic in the literature.
The evidence for MOTS-c is almost entirely preclinical. The original Cell Metabolism study reported improved insulin sensitivity and resistance to diet-induced obesity in mice. A 2021 Nature Communications paper showed that MOTS-c rose in human skeletal muscle and plasma after exercise, and that late-life treatment improved physical capacity in aged mice. Further mouse studies examined ovariectomy-related metabolic dysfunction, bone metabolism, and pancreatic islet senescence. No completed human clinical trial of MOTS-c itself has been published; a modified analog was taken into an early-phase human study by a biotechnology company, with results reported mainly in company communications rather than peer-reviewed papers.
MOTS-c is not approved for any human use in any jurisdiction. In the United States, the FDA placed it in 2023 on its list of bulk drug substances that may present significant safety risks when compounded, stating that the agency had not identified any human exposure data and that immunogenicity and impurity risks could not be assessed. Products sold as MOTS-c are therefore research-grade material or unapproved compounded injections. In sport, MOTS-c has been named on the WADA Prohibited List since the 2024 edition under S4.4, metabolic modulators that activate AMPK, and is prohibited at all times, in and out of competition.
MOTS-c is typically distributed as a lyophilized powder that is reconstituted before subcutaneous injection, and no pharmacokinetic half-life in humans has been established, so the library entry carries no half-life estimate. Storage and beyond-use time therefore follow the dispensed or product label rather than a reference value. A dose log for MOTS-c usually captures vial lot, reconstitution date, concentration, injection site, and any reactions such as palpitations, fever, or injection-site irritation, which are the effects most often reported anecdotally. An inventory record tied to lot numbers is also useful because purity and identity of research-grade material are unverified.
- Category
- Metabolic / mitochondrial
- Routes represented
- Subcutaneous (SubQ)
- Storage context
- Follow the dispensed product or pharmacy label; storage and beyond-use time vary by formulation.
Published literature
Safety evidence
Serious or important: potential immunogenicity, aggregation, impurity, or product-quality risks.
A dependable route-specific human interaction and side-effect profile is not established; this is not evidence of no risk.
Safety evidence sourceCommon questions
Has MOTS-c been tested in humans?
Not in a completed clinical trial of the peptide itself. Human data are limited to observational measurements showing that endogenous MOTS-c rises in muscle and plasma after exercise, and to an early-phase study of a modified analog run by a biotechnology company. USADA and the FDA both note the absence of completed human trials, and the FDA has not identified any human exposure data for compounded MOTS-c products.
Is MOTS-c banned by WADA?
Yes. MOTS-c was added by name to the WADA Prohibited List in the 2024 edition under S4.4.1, activators of AMP-activated protein kinase, within the metabolic modulators class. It is prohibited at all times, meaning both in and out of competition. USADA's explainer on the peptide confirms this status and notes that it is marketed heavily by wellness clinics despite lacking approval.
What does MOTS-c do in the body?
In mouse and cell studies, MOTS-c is a mitochondrial-encoded signaling peptide that activates AMPK by disrupting the folate and methionine cycle, improving glucose uptake and fat oxidation in muscle. It also translocates to the nucleus under stress and regulates genes involved in the antioxidant response. Whether these mechanisms operate at meaningful levels in humans after injection has not been shown.
Is MOTS-c FDA approved?
No. MOTS-c has no approved indication anywhere. In 2023 the FDA listed it among bulk substances that may present significant safety risks in compounding, citing immunogenicity concerns, peptide impurities, and a complete lack of human exposure data. That listing means it is not eligible for routine compounding under section 503A, and any injectable product sold as MOTS-c is unapproved.
Further reading
- Lee et al., Cell Metabolism 2015 (MOTS-c discovery, mouse metabolism)
- Reynolds et al., Nature Communications 2021 (exercise-induced MOTS-c)
- Kong et al., Experimental and Molecular Medicine 2025 (islet senescence, mouse)
- USADA, What is the MOTS-c peptide?
- FDA, bulk drug substances that may present significant safety risks (2023)
Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.
For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.