Unapproved research chemicalNo human evidenceProhibited in sport

MOTS-c

Also referred to as Mitochondrial ORF of the 12S rRNA type-c

An interesting endogenous signalling peptide with genuine mechanistic literature and essentially no human outcome evidence.

Molecule class: Mitochondrial-derived peptide (16 amino acids)
Category: Mitochondrial
Last evidence review: 2026-08-24

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Human studies

Animal / in vitro

Graded claims

—

Participants

Mechanism

What is being studied

Encoded in mitochondrial DNA; reported to influence AMPK signalling and folate-methionine cycle metabolism in the models studied.

Evidence

Claims, graded individually

Each statement below carries its own evidence level, its own confidence rating, and its own account of what remains unestablished. A compound does not have a single grade.

Mitochondrial Research

DPreclinicalLow confidenceNo human evidence

MOTS-c has been reported to influence insulin sensitivity and metabolic markers in mouse models.

What is not established

No adequate human trials. Endogenous presence does not establish that administration is safe or effective.

Supporting sources (2)

Randomised controlled trialHumanIdentifier pending verification

MOTS-c for improving insulin sensitivity in adults with prediabetes and overweight or obesity (MOTS-MET)

Hudson Biotech · Not published · 2026 · n = 120

Population: Adults with prediabetes and overweight or obesity
Endpoint: Treatment-emergent adverse events at 16 weeks; OGTT-derived insulin sensitivity at 12 weeks
Route: Subcutaneous
Quantity as reported: Not disclosed. The registry record states a fixed amount once daily for 12 weeks without naming it.
Frequency: Once daily
Duration: 16 weeks

Result. Recruiting. No results.

Adverse events. Not yet reported.

Limitations. This is the first interventional human study of MOTS-c ever registered, it began in 2026, and it has no results. Until it reports, every MOTS-c quantity in circulation is extrapolated from rodent work.

NCTNCT07505745

Animal studyAnimalIdentifier pending verification

MOTS-c as a mitochondrial-derived peptide in metabolic regulation

Lee C, Zeng J, Drew BG, et al. · Cell Metabolism and related · 2015

Population: Mouse models of diet-induced obesity and insulin resistance
Endpoint: Insulin sensitivity, weight, and metabolic markers
Route: Intraperitoneal in animal models
Quantity as reported: mg/kg in animal models — not translatable
Frequency: Varies

Result. Reported improvement in insulin sensitivity and resistance to diet-induced obesity in the mouse models studied.

Adverse events. Not characterised in humans.

Limitations. Animal and mechanistic work. No adequate human outcome trials.

Search PubMed for this literature →

Last evidence review: 2026-08-23

Human evidence

1 human study catalogued

Human and non-human evidence are kept strictly separate. They are never pooled, averaged, or presented as a single body of support.

Randomised controlled trialHumanIdentifier pending verification

MOTS-c for improving insulin sensitivity in adults with prediabetes and overweight or obesity (MOTS-MET)

Hudson Biotech · Not published · 2026 · n = 120

Population: Adults with prediabetes and overweight or obesity
Endpoint: Treatment-emergent adverse events at 16 weeks; OGTT-derived insulin sensitivity at 12 weeks
Route: Subcutaneous
Quantity as reported: Not disclosed. The registry record states a fixed amount once daily for 12 weeks without naming it.
Frequency: Once daily
Duration: 16 weeks

Result. Recruiting. No results.

Adverse events. Not yet reported.

NCTNCT07505745

Preclinical evidence

Animal and in-vitro research

Kept separate deliberately. Most preclinical findings do not translate to humans, and animal quantities expressed per kilogram do not convert to human quantities by simple arithmetic.

Animal studyAnimalIdentifier pending verification

MOTS-c as a mitochondrial-derived peptide in metabolic regulation

Lee C, Zeng J, Drew BG, et al. · Cell Metabolism and related · 2015

Population: Mouse models of diet-induced obesity and insulin resistance
Endpoint: Insulin sensitivity, weight, and metabolic markers
Route: Intraperitoneal in animal models
Quantity as reported: mg/kg in animal models — not translatable
Frequency: Varies

Result. Reported improvement in insulin sensitivity and resistance to diet-induced obesity in the mouse models studied.

Adverse events. Not characterised in humans.

Limitations. Animal and mechanistic work. No adequate human outcome trials.

Search PubMed for this literature →

Pharmacology

Reported parameters

Half-life

Not characterised

Human pharmacokinetics for administered MOTS-c are not adequately characterised.

Routes studied

Intraperitoneal (animal)
Subcutaneous (non-clinical use)

Evidence from one route does not transfer to another. Topical, oral, and injected administration can produce entirely different exposure from the same quantity.

Regulatory status

Not approved for human use. Prohibited in sport. FDA removed MOTS-c from the Category 2 list effective 22 April 2026, and the Pharmacy Compounding Advisory Committee voted favourably on 23-24 July 2026. Neither is an approval.

Storage as documented

No approved labelling exists.

Safety

Signals reported in the literature

This lists what has been reported. It is not a complete safety profile, and for several compounds in this catalogue no systematic safety surveillance exists at all.

Human safety is not characterised

Limitations

What the evidence cannot tell you

Given as much prominence as the findings, because for most compounds in this category it is the more important half.

Animal and mechanistic work only
Endogenous presence does not imply that administered quantities are safe or effective

Reference

Evidence grading key

AStrong

Multiple high-quality human trials, or strong systematic-review or meta-analytic evidence.

BModerate

Human controlled evidence exists, but replication or sample size is limited.

CPreliminary

Small human studies, observational evidence, or early-phase clinical work.

DPreclinical

Predominantly animal or in-vitro evidence. No adequate human outcome data.

EMechanistic

Biological plausibility or mechanistic reasoning without adequate outcome evidence.

XInsufficient / conflicting

Evidence is absent, irreconcilable, or too weak to support any directional statement.

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