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Ingredients

MOTS-c

MOTSc

Snapshot

IndicationsContraindications
  • Exercise-related metabolic adaptation1
  • Inflammatory lung disease2
  • Cardiometabolic risk marker3
  • Tested competitive athletes4
  • Immunogenicity-prone routes4

Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a microprotein encoded in mitochondrial DNA that regulates metabolic homeostasis and cellular stress responses2. The US Food and Drug Administration (FDA) previously listed it among compounding substances with significant safety risks, the nomination was later withdrawn4, and the World Anti-Doping Agency (WADA) prohibits it at all times4. Interest centers on insulin sensitivity and metabolic disease, exercise adaptation, and inflammatory lung disease2.

Human research is limited to about five small studies, mostly measuring circulating MOTS-c after exercise or heat, or in cancer and type 2 diabetes. Observational data link low circulating MOTS-c with adverse cardiac events in type 2 diabetes with coronary disease. An FDA review for its 2026 compounding advisory committee found a lack of evidence to evaluate effectiveness5. In preclinical models, a 2026 review reports that exogenous MOTS-c attenuated lung injury; no completed human trial has tested it2. The same FDA review covered MOTS-c free base and acetate; see Form comparison5.

The FDA's stated concern is immunogenicity for certain routes and peptide-related impurities, and it identified no human exposure data4.

Last updated October 17, 2026. Read how we make monographs.

In the full monograph

29 sources, 7 studies

  • When to useThe situations practitioners use it for, each with the reason and the study behind it.
  • SafetyWho should avoid it, who needs extra care, and the side effects reported in studies.
  • Protocol notesThe doses used in studies, how and when they were taken, and how the forms on the market compare.
  • How it worksWhat it is and how it works in the body, in plain terms.
  • Published studiesThe studies behind each use, popular claims checked against them, and trials still under way.
  • Word of mouthWhat patients and practitioners report online, kept separate from the clinical evidence.
  • Clinical perspectiveA closing read of where the evidence is solid, where it is thin, and what has not been studied.
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Sources

  1. 1Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review.pubmed.ncbi.nlm.nih.govAyubi, Wibawa, Kurnaz et al. · Physiology international · 2026 · Pubmed
  2. 2MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases.pubmed.ncbi.nlm.nih.govAmado, Agüero, García-Unzueta et al. · Journal of translational medicine · 2026 · Pubmed
  3. 3β-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease.pubmed.ncbi.nlm.nih.govIkonomidis, Katogiannis, Kyriakou et al. · Journal of thrombosis and thrombolysis · 2020 · Pubmed
  4. 4US statusfda.govWhat the FDA (its lists of substances nominated for pharmacy compounding, and Drugs@FDA) and the World Anti-Doping Agency's Prohibited List say about this ingredient, in their own words. A legal status, not evidence of benefit or harm
  5. 5FDA actionsfda.govFDA warning letters, import alerts and Pharmacy Compounding Advisory Committee documents that name this ingredient, in the FDA's words. Findings about products sold and a regulator's review, not evidence of harm from the ingredient itself