Peptide Evidence Index
MOTS-c
Quick answers
- What is it?
- MOTS-c is a small peptide the body's own mitochondria produce, encoded in a short reading frame of mitochondrial DNA. It has never been approved as a medicine and no verified human trial has ever given a person MOTS-c.
- Why are people interested in it?
- It's marketed for metabolism, insulin resistance, and longevity based on promising mouse research, so people want to know if any of that has been tested in humans.
- What has actually been studied?
- In mice, administered MOTS-c has repeatedly improved insulin sensitivity and muscle mitochondrial function; in humans, researchers have only measured people's own naturally occurring MOTS-c levels — in exercise, PCOS, and other conditions — without ever giving anyone MOTS-c as a treatment.
- How strong is the evidence?
- Animal-only: no genuine human trial has ever administered MOTS-c to a person, and one registry record that appeared to be an early human trial shares the hallmarks of fabricated listings identified elsewhere.
- What don't we know yet?
- Whether any of the mouse metabolic effects occur in humans at all, what a safe or effective human dose would be, and whether the one registered 'clinical trial' of MOTS-c is genuine or another fabricated record.
- Where can I read the original research?
- Sources at the bottom of this page: von Walden et al., Journal of Applied Physiology 2021; Yoon et al., Diabetes & Metabolism Journal 2022.
Plain-English overview
MOTS-c is a 16-amino-acid peptide the body already makes on its own, encoded by a short reading frame inside mitochondrial DNA rather than derived from an existing protein fragment. It has never been approved as a medicine, and there is no verified, completed human clinical trial in which a person was given MOTS-c as a treatment. Almost everything known about administering MOTS-c comes from mouse studies, where it has been reported to improve insulin sensitivity, activate the cellular energy-sensing pathway AMPK, and boost skeletal-muscle mitochondrial function. The human research that exists is a different kind of study entirely: researchers have measured the MOTS-c that people's own bodies already produce — after exercise, in polycystic ovary syndrome, and in other conditions — without ever administering it as a drug. One ClinicalTrials.gov record describing an apparent early human trial of MOTS-c shares its sponsor, single site, investigator, and completion date with other registry records already identified elsewhere as fabricated template listings, so it should not be treated as evidence of a genuine ongoing trial.
What researchers are studying it for
- insulin resistance and prediabetes (animal studies; one unverified human trial record)
- exercise performance and metabolic adaptation (animal studies; human data limited to observing endogenous levels)
- obesity and fatty liver (animal studies only)
- aging and longevity (animal studies only)
Current evidence level
Regulatory status: Not an approved medicine. Evidence strength and approval are scored separately; approval is a regulatory decision about a specific use, not a measure of how much research exists.
Human research
No genuine, verified human clinical trial has ever given a person MOTS-c. The human research that exists instead measures MOTS-c that people's bodies already produce naturally. Circulating MOTS-c levels have been measured before and after exercise in healthy adults — one study found acute endurance exercise stimulated circulating MOTS-c in humans (von Walden et al., Journal of Applied Physiology, 2021). A related review summarized this exercise-and-mitohormesis literature, noting that the metabolic effects attributed to MOTS-c mostly come from animal administration studies, while the human data are limited to observing levels the body already makes (Yoon et al., Diabetes & Metabolism Journal, 2022). A case-control study found women with polycystic ovary syndrome had reduced serum and skeletal muscle MOTS-c levels compared with matched controls, again an observational, not interventional, finding (Kutuk et al., Scientific Reports, 2026). One ClinicalTrials.gov record, a Phase 2a study of MOTS-c for prediabetes and obesity (NCT07505745), does name the peptide as an investigational treatment — but its sponsor, single trial site, and listed investigator are identical to those in other registry records already identified elsewhere as fabricated template listings, with a near-identical completion date, so it should not be treated as evidence that a genuine human trial is underway. Separately, other registered, real observational studies measure endogenous MOTS-c as a biomarker — for example, tracking whether MOTS-c levels predict mortality in people with diabetes and coronary artery disease — without ever administering it as a treatment.
Animal and preclinical research
In diet-induced obese mice and in transgenic mouse models, administered MOTS-c has been reported to improve insulin sensitivity, activate the cellular energy-sensing pathway AMPK, boost skeletal-muscle mitochondrial function, and reduce markers of oxidative stress (Gudiksen et al., Free Radical Biology & Medicine, 2026). This is real preclinical work, but it is animal data, not human data, and the same study's human portion was limited to observational measurements rather than administering MOTS-c to people.
Major findings
- In diet-induced obese and transgenic mice, administered MOTS-c has improved insulin sensitivity, activated the AMPK energy-sensing pathway, and boosted skeletal-muscle mitochondrial function (Gudiksen et al., 2026).
- In humans, acute endurance exercise was found to stimulate circulating levels of the body's own naturally occurring MOTS-c (von Walden et al., 2021).
- Women with polycystic ovary syndrome had lower circulating and muscle MOTS-c levels than matched controls, an observational finding (Kutuk et al., 2026).
- A review of the exercise and MOTS-c literature concluded that the metabolic benefits described for MOTS-c are drawn from animal administration studies, while human data are limited to observing endogenous levels (Yoon et al., 2022).
- No genuine, verified human clinical trial has ever administered MOTS-c to a person.
- A ClinicalTrials.gov record for a Phase 2a MOTS-c trial (NCT07505745) shares identical sponsor, site, and investigator details with other fabricated template listings, and should be treated as unverified.
What has not been established
- Whether any of the metabolic effects seen in mice occur in humans at all.
- What a safe or effective human dose would be, since none has ever been tested.
- Whether the one registered 'clinical trial' of MOTS-c is a genuine research effort or another fabricated registry record.
- What happens with repeated or long-term use, since even the animal studies are relatively short.
- What purity or content an unregulated vial sold online actually contains.
Important limitations
- No genuine human interventional trial of MOTS-c exists, so every claim about effects in people rests on animal data or on observing naturally occurring levels.
- The one registry record that would test this in humans shares red flags (identical sponsor, site, investigator, and completion date) with confirmed fabricated listings elsewhere.
- Human observational studies show correlations with the body's own MOTS-c levels, which is not the same as evidence that administering more MOTS-c would do anything.
- The animal literature spans different disease models (obesity, diabetes) using different mouse strains, which limits how consistently any one effect has been replicated.
- Figures used for human dosing online are extrapolated from mouse studies using unvalidated conversion formulas.
Regulatory status
MOTS-c has never been approved as a medicine anywhere. No completed, verified human clinical trial exists.
Primary research sources
- von Walden F, et al., "Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans"
- Journal of Applied Physiology 2021; PMID 34351816, DOI 10.1152/japplphysiol.00706.2019
- Yoon TK, et al., "Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)"
- Diabetes & Metabolism Journal 2022; PMID 35656563, DOI 10.4093/dmj.2022.0092
- Kutuk IS, et al., "Reduced serum and skeletal muscle MOTS-c levels in women with polycystic ovary syndrome"
- Scientific Reports 2026; PMID 41680431, DOI 10.1038/s41598-026-39687-x
- Gudiksen A, et al., "MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner"
- Free Radical Biology & Medicine 2026; PMID 41520850, DOI 10.1016/j.freeradbiomed.2026.01.002
Full evidence entry (complete data, registry records, dosing evidence)
At a glance
- Also known as
- MOTS-c, Mitochondrial Open Reading Frame of the 12S rRNA-c
- Class
- Endogenous mitochondrial-derived peptide (16-amino-acid microprotein)
- Derived from
- A peptide naturally encoded within a short reading frame of the mitochondrial 12S rRNA gene — not derived from an existing protein fragment, but discovered as a distinct signaling molecule mitochondria themselves produce
- Registered human trials
- 0 genuine interventional trials. One record naming MOTS-c is registered on ClinicalTrials.gov, but its sponsor, single site, and investigator are identical to those in at least three other registry records already identified elsewhere on this site as fabricated template listings, with a near-identical completion date — see note below
- …with published results
- 0
- Largest human trial
- None. No human has ever been dosed with MOTS-c in a verified, completed clinical trial. Human data is limited to observational studies measuring people's own naturally occurring MOTS-c levels.
- Studied for
- insulin resistance and prediabetes (animal studies; one unverified human trial record), exercise performance and metabolic adaptation (animal studies; human data limited to observing endogenous levels), obesity and fatty liver (animal studies only), aging and longevity (animal studies only)
- Dosing evidence
- No human dose establishedNo human trial has ever administered MOTS-c to a person, so no human dose exists. Figures circulating online are extrapolated from mouse studies using dose-conversion assumptions never tested in people.
- Regulatory status
- Never approved as a medicine anywhere. No completed, verified human clinical trial exists.
What it is
MOTS-c is a small peptide the body already makes on its own — it's encoded by a short reading frame inside mitochondrial DNA, the genetic material inside the cell's energy-producing organelles, rather than being derived from an existing protein the way many research peptides are. It's one of a handful of recently discovered "mitochondrial-derived peptides" thought to act as signals between mitochondria and the rest of the cell.
It has never been approved as a medicine, and there is no verified, completed human clinical trial of it — a point worth stating plainly given how it's marketed.
What the studies actually found
Almost everything known about giving MOTS-c as a treatment comes from mouse studies. In diet-induced obese mice and in transgenic mouse models, administered MOTS-c has been reported to improve insulin sensitivity, activate the cellular energy-sensing pathway AMPK, boost skeletal-muscle mitochondrial function, and reduce markers of oxidative stress. All of this is animal data, not human data.
The human research that exists is a different kind of study entirely: rather than giving people MOTS-c and observing an effect, researchers have measured the MOTS-c that people's own bodies already produce, under various conditions. Circulating MOTS-c has been measured before and after exercise in healthy adults, in people with cerebral palsy, in women with polycystic ovary syndrome (who had lower levels than matched controls), in marathon runners, and in breast cancer patients on metformin. These are observational studies — they describe correlations with a naturally occurring peptide, not the effect of administering it as a drug.
What exists in humans
No genuine, verified clinical trial has ever given a human MOTS-c. One record on ClinicalTrials.gov, a Phase 2a study of MOTS-c for prediabetes and obesity (NCT07505745), does name the peptide as an investigational treatment — but its sponsor ("Hudson Biotech"), its single trial site (Peking University Shenzhen Hospital), and its listed investigator (Zhen J Peng, PhD) are identical to those in at least three other ClinicalTrials.gov records already identified elsewhere on this site as fabricated template listings rather than real studies, and it carries a near-identical completion date. Because of that shared signature, this record should not be treated as evidence that a genuine human trial of MOTS-c is underway.
Separately, a small number of registered, real observational studies measure endogenous MOTS-c as a biomarker — for instance, tracking whether MOTS-c levels predict mortality in people with diabetes and coronary artery disease, or how anesthesia type affects MOTS-c levels during kidney transplant surgery. These studies do not involve giving anyone MOTS-c.
What doses have been studied in humans
None. No human has received MOTS-c as an administered treatment in a verified clinical trial, so there is no human dose to report.
The figures that circulate in online forums and vendor marketing are derived from the mouse studies described above, converted to a human-equivalent amount using body-surface-area or weight-based scaling formulas. Those formulas estimate comparable exposure between species; they are not evidence that the resulting amount does anything, or is safe, in a person. That conversion has never been tested for MOTS-c specifically.
What remains unknown
- Whether any of the metabolic effects seen in mice occur in humans at all
- What a safe or effective human dose would be, since none has ever been tested
- Whether the one registered "clinical trial" of MOTS-c is a genuine, if very early, research effort or
another fabricated registry record — this page treats it as unverified pending further evidence
- What happens with repeated or long-term use, since even the animal studies are relatively short
- What purity or content an unregulated vial sold online actually contains
Registry and study records
- Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans
- PubMed · von Walden et al., 2021, Journal of Applied Physiology. Observational; measures endogenous MOTS-c, does not administer it. DOI: 10.1152/japplphysiol.00706.2019
- Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)
- PubMed · Yoon et al., 2022, Diabetes & Metabolism Journal (review). Effects described are from animal administration studies. DOI: 10.4093/dmj.2022.0092
- Reduced serum and skeletal muscle MOTS-c levels in women with polycystic ovary syndrome
- PubMed · Kutuk et al., 2026, Scientific Reports. Observational case-control; measures endogenous levels only. DOI: 10.1038/s41598-026-39687-x
- MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner
- PubMed · Gudiksen et al., 2026, Free Radical Biology & Medicine. Administration effects shown in transgenic mice; human portion of the study is observational only. DOI: 10.1016/j.freeradbiomed.2026.01.002
- MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity
- ClinicalTrials.gov NCT07505745 · Template record, not a real study - one of eight Hudson Biotech entries sharing a single site and completion date
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Evidence last reviewed: September 2026. Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.