MOTS-c
Also called Mitochondrial open reading frame of the 12S rRNA-c
A 16-amino-acid peptide encoded by mitochondrial DNA, studied for energy metabolism, insulin sensitivity and exercise. The strongest treatment findings come from cells and animals; a human trial is registered but has no results yet.
Overview
What it is
A mitochondrial-derived peptide discovered in 2015. It is not a steroid or a GLP-1 medicine. CB4211 is a related but distinct investigational analogue.
How it works
In the original experiments, MOTS-c affected the folate cycle and purine metabolism and activated AMPK, the cell's energy sensor. Treated mice were protected against some diet- and age-related loss of insulin sensitivity.
What the research shows
A 2021 study linked MOTS-c to the exercise response and improved physical function in young and old mice. A 2026 study found it rose in fluid around working human muscle during exercise. The MOTS-MET phase 2a trial (NCT07505745, about 120 people, 12 weeks) is studying insulin sensitivity with no results posted. A completed phase 1 trial of the analogue CB4211 (NCT03998514) also has no posted results.
Studied for
- Insulin sensitivity and obesitymice
- Physical decline with agemice
- Natural levels during exercisehuman observation
- Insulin sensitivityphase 2a, ongoing
Safety and regulatory status
Safety and side effects
Human side-effect rates are unknown. FDA's 2026 staff review cited gaps in human data and concerns about immune reactions, aggregation and impurities. Occurring naturally in the body does not make a manufactured product safe.
Regulatory status
Not FDA approved. Reviewed by FDA's Pharmacy Compounding Advisory Committee in July 2026, which is not drug approval.
Mixing and dosing reference
Reference information only. Read before using this section.
MOTS-C (20 mg Vial) Dosage Protocol
- Vial
- 20 mg MOTS-C
- Add diluent
- 3 mL
- Concentration
- 6.67 mg/mL
- 1 unit (U-100)
- 66.67 mcg in 0.01 mL
- Route
- Subcutaneous
- Typical range
- 200–1,000 mcg once daily (gradual titration over 10 weeks).
Community-reported use
| Week | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 200 mcg (0.2 mg) | 3 units (0.03 mL) |
| Weeks 3–4 | 400 mcg (0.4 mg) | 6 units (0.06 mL) |
| Weeks 5–6 | 600 mcg (0.6 mg) | 9 units (0.09 mL) |
| Weeks 7–8 | 800 mcg (0.8 mg) | 12 units (0.12 mL) |
| Weeks 9–10+ | 1,000 mcg (1.0 mg) | 15 units (0.15 mL) |
MOTS-C 20 mg Concentration and U-100 Math
| Displayed amount | Calculation | U-100 marking | Liquid volume |
|---|---|---|---|
| 200 mcg | 200 ÷ 66.7 | 3 units | 0.03 mL |
| 400 mcg | 400 ÷ 66.7 | 6 units | 0.06 mL |
| 600 mcg | 600 ÷ 66.7 | 9 units | 0.09 mL |
| 800 mcg | 800 ÷ 66.7 | 12 units | 0.12 mL |
| 1,000 mcg | 1,000 ÷ 66.7 | 15 units | 0.15 mL |
Preclinical MOTS-C Evidence
| Evidence type | What it can address | What it cannot establish |
|---|---|---|
| Cell studies | Signaling pathways and molecular responses | Human vial dose, route, frequency, or safety |
| Animal studies | Model-specific metabolism, performance, and tissue effects | A clinically validated human schedule |
| Human observational exercise studies | Endogenous MOTS-c levels and associations | Effects of an injected 20 mg research vial |
| Regulatory review | Known data gaps and product-quality concerns | A positive safety or efficacy conclusion |
How to mix
- Draw 3.0 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming.
- Gently swirl/roll until dissolved (do not shake vigorously).
- Label with reconstitution date and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light. Follow documented, formulation-specific discard guidance.
Protocol source: PeptideDosages.com
Common questions
Does MOTS-c help with weight loss or belly fat?
That has not been shown in people.
Can it replace exercise?
No. Mouse findings do not show an injection replaces exercise in humans.
Is CB4211 the same as MOTS-c?
No. It is a related analogue; results should not be transferred.
Related in Metabolic Health
Sources and further reading (5)
- Lee C, et al. MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 2015.
- Reynolds JC, et al. MOTS-c is an exercise-induced regulator of age-dependent physical decline. Nat Commun, 2021.
- ClinicalTrials.gov NCT07505745 (MOTS-MET); NCT03998514 (CB4211).
- FDA. MOTS-c bulk drug substances: staff evaluation, July 2026.
- Source summary: PeptideDosages.com research overview (rewritten for NVO).
Laboratory research material: MOTS-C Research Use Only