{"id":"mots-c","name":"MOTS-c","aliases":["mitochondrial ORF of the twelve S rRNA type-c","mitochondrial-derived peptide"],"url":"https://lyoresearch.com/compounds/mots-c","summary":"MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA rather than the nucleus, discovered in 2015. In mice it improves insulin sensitivity and protects against diet-induced obesity, and human blood levels fall with age and correlate with fitness. No controlled human trial has tested giving it to anyone. It is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","outcomes":[{"outcome":"Insulin sensitivity / metabolic health","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Mouse models of diet-induced obesity and insulin resistance. Human data is observational — levels correlate with fitness and fall with age — which cannot show what supplementation would do.","references":[]},{"outcome":"Exercise capacity","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Rodent exercise models; human correlation studies only.","references":[]},{"outcome":"Longevity","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Association studies of a mitochondrial variant in a Japanese cohort; not an intervention.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study of any kind.","references":[]}],"regions":[{"region":"European Union","status":"Unapproved medicinal product","note":"No authorisation; sale for human use is an offence for the seller."},{"region":"United States","status":"Not approved","note":"Sold as a research chemical."},{"region":"Australia","status":"Prescription-only or unapproved","note":"Scheduled by the TGA; not available without a prescription."}],"faq":[{"q":"Does MOTS-c improve metabolism in humans?","a":"Unknown. The metabolic effects are from mouse studies. Human research so far measures naturally occurring MOTS-c levels; it has never been given to people in a controlled trial."},{"q":"Why do people say it is linked to longevity?","a":"A mitochondrial variant affecting MOTS-c has been associated with longevity in a Japanese cohort. That is an association in people who inherited it, not a result of taking anything."}],"references":[{"cite":"Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.","where":"Cell Metab, 2015;21:443–454","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lee+MOTS-c+mitochondrial+derived+peptide+2015+Cell+Metabolism","note":"The discovery paper; mouse models."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. All outcomes graded D on absence of human intervention trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}