MOTS-c 40 mg — Quick Chart
Dosing & Reconstitution Overview
MOTS-c (mitochondrial open reading frame of the twelve S rRNA-c) is a 16-amino-acid mitochondrial-derived peptide studied for its role in metabolic regulation and cellular energy balance. The figures below are compiled strictly for laboratory and educational reference — they describe how the compound has been handled and dosed across published animal and cell studies, not a recommendation for use in humans or animals.
For a 40 mg vial, adding 3.0 mL of bacteriostatic water yields a concentration of roughly 13.33 mg/mL (13,333 mcg/mL). At that concentration, every 0.075 mL drawn on a U-100 insulin syringe equals 7.5 units and delivers about 1000 mcg (1 mg) of material, which keeps the daily microgram-scale arithmetic manageable.
Standard (Gradual) Titration Schedule
The gradual schedule steps the daily amount upward every two weeks, mirroring the slow dose-escalation approach used to model tolerability before reaching the upper end of the studied range.
| Phase | Daily Dose | Units (U-100) | Volume | Frequency |
|---|---|---|---|---|
| Weeks 1–2 | 200 mcg | 1.5 units | 0.015 mL | Once daily |
| Weeks 3–4 | 400 mcg | 3 units | 0.030 mL | Once daily |
| Weeks 5–6 | 600 mcg | 4.5 units | 0.045 mL | Once daily |
| Weeks 7–8 | 800 mcg | 6 units | 0.060 mL | Once daily |
| Weeks 9–10+ | 1000 mcg | 7.5 units | 0.075 mL | Once daily |
Reconstitution Steps
- Let the sealed lyophilized vial and the bacteriostatic water reach room temperature, then wipe both stoppers with an alcohol swab.
- Draw 3.0 mL of bacteriostatic water and inject it slowly down the inside wall of the vial — never directly onto the powder pellet.
- Swirl gently until fully dissolved. Do not shake; aggressive agitation can shear the peptide.
- The solution should be clear and colourless. Label the vial with the concentration (13.33 mg/mL) and the reconstitution date.
- Store upright under refrigeration between uses and draw each daily volume with a fresh sterile syringe.
Supplies Needed
- MOTS-c vials (40 mg): ~1 vial for an 8-week run; ~2 vials for 12 weeks; ~3 vials for 16 weeks at the upper daily steps.
- Insulin syringes (U-100, 1 mL): ~56 for 8 weeks, ~84 for 12 weeks, ~112 for 16 weeks (one fresh syringe per daily draw).
- Bacteriostatic water (10 mL): a single bottle covers the diluent for these durations.
- Alcohol swabs: roughly two 100-count boxes for 8–12 weeks; three boxes for a 16-week schedule.
Protocol Overview
- Research goal: model metabolic and mitochondrial regulation via AMPK activation.
- Schedule: once-daily subcutaneous administration in the published models.
- Dose band: 200–1000 mcg daily across a gradual 10-week escalation.
- Fill: 40 mg lyophilized, reconstituted to 13.33 mg/mL with 3 mL diluent.
- Storage: −20 °C dry; 2–8 °C once reconstituted.
Dosing Protocol Notes
- Begin at the lowest 200 mcg step and hold each level for about two weeks before escalating.
- Keep administration on a fixed daily cadence and around the same time for steady exposure modelling.
- Escalate only after tolerability is established at the prior step.
- The microgram volumes are small (1.5–7.5 units), so draw carefully and confirm the dose against the syringe markings.
Storage Instructions
Keep sealed lyophilized vials at −20 °C or below, protected from light, where stability extends for many months. Once reconstituted, refrigerate at 2–8 °C and use within about seven days. Allow refrigerated solution to warm slightly before drawing, avoid repeated freeze-thaw cycles, and aliquot if a vial will be sampled many times.
Important Handling Notes
- Use a sterile syringe for every draw and never re-enter the vial with a used needle.
- Rotate sampling/handling technique to keep the stopper intact.
- Confirm small microgram volumes carefully against the syringe scale before each draw.
- Document each draw — date, volume, remaining material — for reproducibility.
How MOTS-c Works
MOTS-c is a peptide encoded within the mitochondrial 12S rRNA region and translated from a short open reading frame. Mechanistically it activates AMP-activated protein kinase (AMPK) — a central energy sensor — in part by interfering with the folate-methionine cycle and driving accumulation of AICAR, which pushes cells toward an energy-conserving state. Through this AMPK axis it is reported to enhance glucose uptake, fatty-acid oxidation and mitochondrial respiration while reducing fat storage. It is notable as one of the mitochondrial-derived peptides that signal between mitochondria and the rest of the cell.
Reported Benefits & Side Effects
Benefits observed in preclinical studies
- Improved insulin sensitivity and glucose metabolism in animal models.
- Prevention of diet-induced insulin resistance and reduced visceral fat.
- Increased energy expenditure and enhanced exercise capacity (aged mice ran roughly twice as long).
- Reduced liver fat, improved cardiac function, promotion of bone formation and modulation of immune aging.
Side effects reported
- No adverse effects were reported across the published preclinical (animal and cell) work.
- Human tolerability and safety remain unknown — no completed human clinical trials exist.
- All efficacy signals to date come strictly from laboratory and animal research.
Supporting Lifestyle Factors (Research Context)
- Exercise is a frequent co-variable in MOTS-c studies, since the peptide is itself exercise-responsive.
- Controlled dietary inputs to model glucose and lipid handling in the published designs.
- Standard trial controls — consistent activity, hydration and rest — to isolate the compound's effect.
Injection Technique (Reference Only)
- Clean the vial stopper and the site with alcohol swabs and let them dry completely.
- Pinch a skinfold and insert subcutaneously at 90° (or 45° for very lean tissue); aspiration is not required for subcutaneous work.
- Inject slowly over several seconds given the small volume.
- Rotate sites systematically — abdomen (at least two inches from the navel), outer thighs, upper arms — and dispose of sharps in an approved container.
References
- Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and AMPK activation. Cell Metabolism (2015). ncbi.nlm.nih.gov/pmc/articles/PMC4350682
- Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c and exercise, metabolism and healthspan. Nature Communications (2021). ncbi.nlm.nih.gov/pmc/articles/PMC7817689
- Lu H, Wei M, Zhai Y, et al. MOTS-c and metabolic regulation. Journal of Molecular Medicine (2019). pubmed.ncbi.nlm.nih.gov/30725119
- Wan W, Zhang L, Lin Y, et al. Mitochondrial-derived peptide MOTS-c review. Journal of Translational Medicine (2023). translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03885-2
- Kong BS, Lee H, L'Yi S, et al. MOTS-c and mitochondrial signalling. Experimental & Molecular Medicine (2025). pubmed.ncbi.nlm.nih.gov/40855115