MOTS-c
Mitochondrial-derived peptide
Also MOTSc, MOTS c, Mitochondrial open reading frame of the 12S rRNA type-c, MOTS-c peptide, Mitochondrial-derived peptide
- Evidence
- CAnimal and cell studies
- FDA status
- Not approvedas of 2026-10-26
- Route
- Injection
- Studies cited
- 1 human2 animal or cell
Sold for
MOTS-c is sold as an 'exercise mimetic', a mitochondrial peptide said to burn fat, improve insulin sensitivity, and boost endurance the way training does.
Studies say
Mice given MOTS-c resisted obesity and ran longer, and humans make more of it after exercise, but no trial has given it to people, so the evidence is grade C.
Why grade C. The efficacy data are in mice: the 2015 discovery paper showing protection from diet-induced obesity and insulin resistance, and a 2021 paper showing better physical performance in young and old mice. The only human data measure the body's own MOTS-c rising in muscle and blood after exercise. No human has received MOTS-c in a published trial, so C. 36
FDA. Not approved by the FDA for any use and sold as a research chemical. MOTS-c was nominated for the FDA's compounding bulk-substances list and placed in Category 2 (significant safety risk); the nomination was withdrawn, the FDA removed it from that category in April 2026, and the Pharmacy Compounding Advisory Committee discussed it in July 2026. It is also on the 2026 WADA Prohibited List. 45
Written from 7 cited sources. Last refreshed 2026-10-27. Not physician reviewed.
Evidence checklist
- Randomised controlled trial No trial has given it to peopleno
- Human study over 100 people No human dosing studyno
- More than one research group Mouse work from one lab groupno
- Clinical outcomes, not surrogate markers Mouse outcomes; human data are natural levelsno
- Human safety data beyond case reports No human safety datano
Drawn from the cited studies below. A dash means the sources give no information.
What it is
MOTS-c is a 16-amino-acid peptide encoded not in the cell nucleus but in the mitochondrial genome, within the gene for the 12S ribosomal RNA. Its name stands for mitochondrial open reading frame of the 12S rRNA type-c. It was identified in 2015 by Changhan Lee and Pinchas Cohen's group at the University of Southern California, which had earlier found humanin, the first such mitochondrial-derived peptide. Eight have been described so far. 37
CohBar, a company co-founded by the discoverers, developed a modified analog called CB4211 and ran a phase 1 trial in adults with obesity and fatty liver, but that program ended in 2021 and no result was published in a journal. Unmodified MOTS-c sold online has not been in any registered trial. 17
How it works
MOTS-c acts mainly in skeletal muscle. It inhibits the folate cycle and the linked synthesis of purines, which raises AMP and activates AMPK, the energy-sensing enzyme that exercise also switches on. AMPK activation increases glucose uptake into muscle through GLUT4 transporters and shifts cells toward burning fat. Under metabolic stress MOTS-c also moves into the nucleus and changes gene expression. This is the basis for calling it an exercise mimetic. 23
What human research shows
Humans have been studied only as producers of their own MOTS-c. In the 2021 Nature Communications paper, a bout of exercise raised MOTS-c in skeletal muscle and in blood plasma in healthy volunteers, and levels fell during recovery. No published trial has given MOTS-c to humans; claims about fat loss, endurance, or insulin sensitivity in people rest entirely on the mouse studies. 36
| Study | Model | Finding |
|---|---|---|
| MOTS-c discovery and metabolic effects (Lee 2015) | Mice and cell culture | MOTS-c prevented diet-induced obesity and age- and diet-related insulin resistance via AMPK activation in muscle. 3 |
| MOTS-c and physical performance in aging mice (Reynolds 2021) | Mice (young, middle-aged, old) plus human exercise biopsies | Treated mice ran longer at every age, and late-life treatment improved physical capacity; exercise raised endogenous MOTS-c in human muscle and plasma. 6 |
| Mitochondria-derived peptides review (Miller 2022) | Review of animal and human observational data | Summarizes eight known mitochondrial-derived peptides and the absence of interventional human trials. 7 |
Safety
There are no human safety data for administered MOTS-c. In mice, the published studies report no toxicity, but they were efficacy studies, not safety studies. The FDA's earlier Category 2 placement cited the absence of human data and poor characterization of the products being sold; Public Citizen testified against listing it for compounding at the July 2026 advisory committee meeting on the same grounds. 4
Athletes should know that MOTS-c is explicitly named on the 2026 WADA Prohibited List under metabolic modulators, and has produced positive doping tests. 5
Questions for your clinician
- Is there any controlled human trial of administered MOTS-c?
- Does the mouse research apply to people?
- Is MOTS-c banned in my sport?
Questions people ask
Has MOTS-c gained any regulatory approval?
No. It has no approval and has never been in a published human trial. It can be sold as a research chemical not for human use, compounding pharmacies may not prepare it, and it is banned in sport under the 2026 WADA Prohibited List. 45
What have studies found so far?
In mice it improved insulin sensitivity, prevented obesity on a high-fat diet, and extended running capacity. In humans the only data are that exercise raises the body's own MOTS-c. 36
How does MOTS-c compare with humanin?
Both are peptides encoded in mitochondrial DNA. Humanin, found first, has been studied mostly for protecting cells from stress and in neurodegeneration; MOTS-c has been studied mostly for muscle metabolism. 7
Citations
- Front Endocrinol 2023: Review of MOTS-c in metabolism and disease doi.org
- Biochim Biophys Acta 2021: Mitochondrial-derived peptides and exercise doi.org
- Lee 2015, Cell Metab: The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance pubmed.ncbi.nlm.nih.gov
- FDA: Certain bulk drug substances for use in compounding may present significant safety risks fda.gov
- WADA: 2026 Prohibited List wada-ama.org
- Reynolds 2021, Nat Commun: MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline pubmed.ncbi.nlm.nih.gov
- Miller 2022, J Clin Invest: Mitochondria-derived peptides in aging and healthspan pubmed.ncbi.nlm.nih.gov