MOTS-c is a 16-amino-acid peptide encoded inside mitochondrial DNA rather than in the cell nucleus, which is what makes it unusual. It was first described in 2015 as promoting metabolic homeostasis, acting largely through the AMPK pathway - the same energy-sensing pathway that exercise and metformin act on.

Is there human evidence for MOTS-c?

Yes, but not the kind most people assume. The human studies measure the MOTS-c your own body produces, and show it rising in response to endurance exercise, resistance exercise, metformin and heat stress. They are studies of MOTS-c as a biomarker, not studies of MOTS-c as a drug.

Has anyone tested injecting MOTS-c in people?

One placebo-controlled trial giving subcutaneous MOTS-c to adults with prediabetes is currently recruiting. It has not reported results. As of this page, no completed human trial has tested injected MOTS-c for insulin sensitivity, fat loss, performance or aging.

What is the correct MOTS-c dosage?

No dose has been validated by a completed human efficacy trial. A Phase 2 study of 120 people is currently testing a fixed once-daily subcutaneous dose over 12 weeks, with primary completion due in February 2027, and its registry entry does not publish the milligram amount. The figures in dosage charts and calculators are extrapolations from rodent studies and from human exercise research where nobody was injected with anything.

Is MOTS-c allowed in sport?

No. It is a prohibited substance, and USADA has published guidance on it specifically. Treat any vendor claim to the contrary as a reason to distrust everything else on that page.

Research peptides

MOTS-c: The Human Studies Are About Exercise, Not Injections

Every MOTS-c protocol online gives you milligrams. The human research measures your own MOTS-c rising after exercise. That gap is the whole story of this compound.

Written bySebastian Hunter, Founder and Editor

Published August 23, 2026

Start here

Plain English

MOTS-c is a small peptide your own mitochondria make. Human studies measure it going up when you exercise. They do not test injecting it - one trial that does is still recruiting and has reported nothing. The dosing charts you have seen are extrapolated from rodents and from exercise studies.

Your body already makes it. Exercise raises it.
No completed human trial has tested injecting MOTS-c. A Phase 2 trial reports in 2027.
It is not approved for human use, and it is prohibited in sport.

Search for MOTS-c dosage and you will find charts, calculators, injection schedules, and pages titled things like “the exact protocol we use”. They are remarkably specific: milligrams per injection, days between doses, cycle lengths, what time of night to inject.

Then you read the human research, and it is about exercise.

What MOTS-c is

MOTS-c is a 16-amino-acid peptide encoded not in the cell nucleus but inside mitochondrial DNA itself, in the 12S rRNA region. That is genuinely unusual and is most of why it drew attention. It was described in 2015 as promoting metabolic homeostasis, acting largely through AMPK Lee 2015 - Lee C, Zeng J, Drew BG et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-54. (opens PubMed in a new tab) — the same energy-sensing pathway that exercise and metformin work on.

The mechanistic and preclinical literature since then is substantial, and reviews cover its proposed roles in metabolism, insulin sensitivity and aging Zheng 2023 - Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. (opens PubMed in a new tab) Kong 2023 - Kong BS, Lee C, Cho YM. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes Metab J. 2023;47(3):315-324. (opens PubMed in a new tab).

What the human studies actually did

This is the part that matters, and it is not what the protocol sites imply.

PubMed returns four MOTS-c records tagged as randomised controlled trials. Not one of them gave anybody MOTS-c. They measured the MOTS-c people already had:

Acute endurance exercise raised circulating mitochondrial-derived peptides in humans von 2021 - von Walden F, Fernandez-Gonzalo R, Norrbom J et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985). 2021;131(3):1035-1042. (opens PubMed in a new tab).
Aerobic and resistance exercise affected MOTS-c levels Dieli-Conwright 2021 - Dieli-Conwright CM, Sami N, Norris MK et al. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Sci Rep. 2021;11(1):16916. (opens PubMed in a new tab).
Metformin treatment was associated with circulating MOTS-c levels in breast cancer patients Cuyàs 2022 - Cuyàs E, Verdura S, Martin-Castillo B et al. Circulating levels of MOTS-c in patients with breast cancer treated with metformin. Aging (Albany NY). 2022;15(4):892-897. (opens PubMed in a new tab).
Repeated heat stress modulated MOTS-c in active men Elhusseiny 2025 - Elhusseiny R, Ihsan M, Labidi M et al. Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization. Med Sci Sports Exerc. 2025;57(12):2764-2774. (opens PubMed in a new tab).

Human MOTS-c studies, by what the study actually did

Exercise, MOTS-c measuredendurance, resistance, heat stress
3
Metformin, MOTS-c measuredbreast cancer patients
1
MOTS-c given, completedno results exist to report
0
MOTS-c given, in progressPhase 2, reports February 2027
1

Counts of the human studies discussed on this page. The distinction that matters is not how many there are but which direction they run: in the top two groups MOTS-c is what gets measured and the intervention is something else, and the bottom two are the only studies that give it to anyone.

The one trial that does inject it

There is a placebo-controlled trial administering subcutaneous MOTS-c to adults with prediabetes, measuring insulin sensitivity. It is recruiting. It has not reported anything.

That trial is the reason to keep an eye on this compound rather than dismiss it. It is also the reason nobody can honestly tell you today what injected MOTS-c does in a human being, because the study designed to answer that question is still enrolling people.

What is known about dose

We publish doses where a study establishes one. For MOTS-c in humans, here is the complete honest answer: there isn’t one yet, and here is exactly when there might be.

The Phase 2 trial described above enrols 120 participants, gives a fixed dose once daily by subcutaneous injection for 12 weeks, and lists primary completion in February 2027. The registry entry does not publish the milligram amount.

So the state of play is that the one study designed to establish a human dose is running, is blinded, and has not reported. Everything circulating today predates it.

Where the charts actually come from

Rodents, and inference. The protocols agree with each other closely, which reads like corroboration and is mostly copying. Where a number traces to anything it traces to animal studies at doses scaled by bodyweight, or to a clinician’s practice, or to another website.

Several of the sites publishing dosage charts say this themselves — that no dose has been validated in a completed human efficacy trial — a few paragraphs below the chart.

Status: not approved, and banned in sport

US legal status - Research use only · not for human use

Sold for laboratory research use only. Not approved by the FDA for human use, and cannot be lawfully marketed as a supplement or a medicine. Products sold this way are not made to pharmaceutical quality standards, and their contents are not verified by anyone.

MOTS-c is not approved for human use. It is sold as a research chemical, which is the legal basis on which a vendor can sell it at all, and products in that channel are not made to pharmaceutical quality standards — nobody verifies what is in the vial.

It is also prohibited in sport, and USADA has published guidance on MOTS-c specifically. If you are tested, this is not a grey area, and a vendor page telling you otherwise has told you something useful about that vendor.

References

Bibliographic detail is fetched from PubMed, not written by us - so a citation here cannot drift from the paper it names. Study design comes from PubMed's own tags rather than our judgement.