MOTS-c
Mitochondrial-Derived Peptide (16-amino acid)
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that acts on AMPK, the cell's energy sensor. It is studied for insulin sensitivity, obesity and age-related decline in physical function. Evidence comes from mouse and cell studies; no human trial has tested MOTS-c doses.
Quick reference
How MOTS-c is dosed in practice
Protocols use 5–15 mg of MOTS-c a week in total, injected SubQ and split into 2 or 3 doses — for example 2.5–5 mg two or three times a week. The ranges in this guide never exceed 10 mg in a single injection or 3 injections a week.
Many start at the low end (around 5 mg a week) and run 8 weeks on, 4 weeks off. Some inject before exercise or in a fasted state; that timing idea comes from mouse data, not human testing.
Where the numbers come from: no human trial has tested MOTS-c doses. These ranges are practitioner convention built on mouse studies.
Work out the units to draw with the reconstitution calculator and how long a vial lasts with the vial duration calculator.
How MOTS-c works
MOTS-c is a mitochondrial-derived peptide — encoded in the 12S rRNA region of mitochondrial DNA. It is one of a small number of peptides made from mitochondrial genes, and it is thought to act as a signal from the mitochondria to the rest of the cell.
In mouse and cell studies, MOTS-c activates AMPK (the cell's energy sensor), improving glucose uptake into muscle and increasing fat burning. Metformin also acts through AMPK, by a different route.
In mice, MOTS-c prevented diet-induced obesity and insulin resistance, and a later study found it improved physical capacity in older mice. In people, MOTS-c levels rise naturally with exercise. Whether injected MOTS-c has any of these effects in humans hasn't been tested.
Why it's paired with GLP-1 drugs: practitioners add MOTS-c to a stable GLP-1 dose on the idea that better cellular energy use complements lower calorie intake. That pairing has not been tested in people. In the DoseCraft framework, MOTS-c is filed under ATP Shortage and Insulin Resistance.
Reconstitution math
- Remove the flip-off cap from the 10 mg vial.
- Draw 1 mL of bacteriostatic water into a sterile syringe.
- Inject slowly down the vial wall.
- Swirl gently. Do not shake.
- Refrigerate. Stable approximately 4 weeks at 2–8°C.
Dose math
10 mg vial + 1 mL bac water → 10 mg per mL (10,000 mcg/mL).
On a 100-unit insulin syringe (1 IU = 0.01 mL):
- • 25 IU = 2.5 mg (2,500 mcg)
- • 50 IU = 5 mg (5,000 mcg)
- • 100 IU = 10 mg (10,000 mcg) — the most for a single injection
Synergy stack
MOTS-c + Tirzepatide / Semaglutide — metabolic pairing
Practitioners sometimes add MOTS-c after someone has been on a stable GLP-1 dose for a while, reasoning that MOTS-c's effects on cellular energy use (seen in mice) complement the lower calorie intake from the GLP-1 drug. The combination has not been tested in people.
MOTS-c protocol
5–15 mg per week total (2–3 injections)
Use case
Added after ~8 weeks on a stable GLP-1 dose (convention)
Safety + side-effect profile
There is no human safety trial for injected MOTS-c. Effects people report are mostly mild and short-lived.
Unknown, not ruled out: long-term effects of injecting it. Avoid with: active cancer, pregnancy, breastfeeding. Use caution with insulin or sulfonylureas, since added glucose-lowering is possible.
Interaction notes: commonly combined with GLP-1 drugs, BPC-157 and GHK-Cu, without interaction studies. Use caution combining it with other AMPK-acting compounds (metformin, berberine) without medical supervision.
- • Mild warmth after injection (passes within about 30 minutes)
- • Occasional mild tiredness in the first week
- • Low blood sugar in people on glucose-lowering medicines
- • Rare injection-site soreness
Frequently asked
What is MOTS-c?
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that activates AMPK, the cell's energy sensor. In mice it improved insulin sensitivity and prevented diet-induced obesity. No human trial has tested MOTS-c doses.
What is the typical MOTS-c dose?
Most protocols use 5–15 mg a week in total, injected SubQ and split into 2–3 doses (for example 2.5–5 mg each). Cycles are commonly 8 weeks on, 4 weeks off. These are practitioner conventions — no human trial has tested MOTS-c doses — and the ranges here never exceed 10 mg per injection or 3 injections a week.
How do I reconstitute MOTS-c?
10 mg vial + 1 mL bacteriostatic water → 10 mg/mL. On a 100-unit insulin syringe, 25 IU = 2.5 mg, 50 IU = 5 mg, 100 IU = 10 mg. Refrigerate after reconstitution; use within about 4 weeks.
Why stack MOTS-c with GLP-1 agonists?
Practitioners pair them on the idea that MOTS-c's effects on cellular energy use (seen in mice) complement the lower calorie intake from GLP-1 drugs. The combination hasn't been tested in people, so any added fat loss is unproven.
Is MOTS-c the same as metformin?
No. Both act on AMPK, but by different routes, and metformin is an approved drug with decades of human data while MOTS-c has none. Don't replace a prescribed medicine with MOTS-c; if you take both, involve your prescriber.
Are there MOTS-c side effects?
Reported effects are generally mild: warmth after injection, occasional tiredness in the first week, low blood sugar in people on glucose-lowering medicines, and rare injection-site soreness. There is no human safety trial.
Should I cycle MOTS-c?
The common convention is 8 weeks on, 4 weeks off. There is no trial evidence on cycling.
Will MOTS-c affect my bloodwork?
There are no human data on what MOTS-c does to bloodwork. If you want to track it, fasting glucose, HbA1c and lipids before and after a cycle are reasonable markers to discuss with your clinician.
Related compounds
Often researched, stacked, or compared with MOTS-c.
Cited research
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 2015.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun, 2021.
Page updated · How we grade evidence
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