Dr. Pep

Peptides · Mitochondrial-derived peptide

MOTS-c: what the studies show

Every line below comes from a study, label or regulator record, checked by two models, with the source linked. Information, not medical advice. For adults 18+.

What it is

  • MOTS-c is a 16-amino-acid peptide the body makes from a short gene inside mitochondrial DNA (the 12S rRNA region). It was first reported in 2015.[1][2]
  • Because it is a natural molecule, most human papers on MOTS-c simply measure the person's own blood or muscle levels in disease, exercise or ageing. Such studies are not evidence that injecting MOTS-c works. Directions are even mixed: levels are reported lower in some conditions and higher in others.[3][4][5][6]
  • A drug-company analogue called CB4211 (a different molecule from the MOTS-c sold online) reached early human trials. A review states that its phase 1a showed it was safe and well tolerated after seven days of dosing.[7][8]

Bottom line

  • MOTS-c has no published human trial of injected MOTS-c in these records. Its metabolic and exercise effects come from mice, rats and cell culture, mostly doses of 5 to 15 mg/kg a day injected into mice. FDA's own review found no human data by any route.[2][9]

What the human studies found

  • FDA's briefing document (evaluation for the July 23-24, 2026 advisory committee) found no studies of compounded MOTS-c in humans and no information on MOTS-c given to humans by any route.[2]
  • Human studies that measure natural MOTS-c: a randomised exercise study (30 people, 10 per group) found acute endurance exercise showed only a trend to raise plasma MOTS-c. In healthy men aged 18 to 81, circulating MOTS-c fell with age while muscle MOTS-c was about 1.5-fold higher in older men than young. In a case-control study of 400 people (healthy controls, unstable angina and heart attack), serum MOTS-c was higher in those with acute coronary syndrome than in controls. A 2024 meta-analysis (7 studies, 602 people) found lower plasma MOTS-c in type 2 diabetes (SMD -0.89) but higher levels in obesity (SMD 0.51). None of these gave anyone MOTS-c.[6][5][4][3]
  • Several records labelled 'human RCT' (grade A) in the records we hold are exercise, heat-stress or metformin trials that only measured MOTS-c levels. They are not trials of MOTS-c as a treatment.[6][10][11]

Known risks and side effects

  • Human safety is unknown. FDA said it is particularly concerned about the lack of human data by any route, and that immune-reaction risk from impurities and aggregation cannot be ruled out for injected peptides.[2]
  • FDA also found no nonclinical data to inform safety for potential clinical uses.[2]
  • MOTS-c is listed as a prohibited substance in the Global DRO database drawn from the 2024 WADA Prohibited List.[2]

Legal status

  • As of 2026-10-09 MOTS-c is not approved. FDA's category 2 page lists MOTS-c among nominated-but-withdrawn substances, noting no human exposure data and significant immunogenicity concern.[12]
  • FDA's briefing document for the July 23-24, 2026 advisory committee proposed not adding MOTS-c (free base or acetate) to the 503A bulks list, citing poor characterisation, unknown use in compounding, and no clinical studies of safety or effectiveness.[2]
  • ABC News reportedly said the committee narrowly voted to recommend adding MOTS-c and five other peptides to the 503A list despite FDA staff opposition. This is a secondary report. FDA had not posted the outcome as of 2026-10-09. The vote is advisory and non-binding.[13]

Sources

  1. [1] The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.
  2. [2] July 23-24, 2026, Meeting of the Pharmacy Compounding Advisory Committee – FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate)
  3. [3] The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis.
  4. [4] Circulating Mitochondrial Open Reading Frame of the 12S Ribosomal RNA Type-c Is Higher in Acute Coronary Syndrome and Is a Prognostic Biomarker for Major Cardiac Events in Patients With Acute Myocardial Infarction: A Case-Control Study.
  5. [5] Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition.
  6. [6] Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans.
  7. [7] Effects of Mitochondrial-Derived Peptides (MDPs) on Mitochondrial and Cellular Health in AMD.
  8. [8] Mitochondria-derived peptides in aging and healthspan.
  9. [9] MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.
  10. [10] Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization.
  11. [11] Circulating levels of MOTS-c in patients with breast cancer treated with metformin.
  12. [12] FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (503A/503B category 2)
  13. [13] ABC News: FDA advisers narrowly vote to add 6 peptides to drug compounding list (2026-07-24)