A 16-amino-acid peptide encoded in mitochondrial DNA, studied in mice for insulin sensitivity, fat gain and exercise capacity.
Also called Mitochondrial open reading frame of the 12S rRNA type-c, MOTSc, CB4211 (a modified analog, not MOTS-c itself)
MOTS-c is a small peptide your own cells make. The instructions for it sit inside mitochondrial DNA, in the gene for the 12S ribosomal RNA, which is unusual: almost every protein in the body is coded in the nucleus. It was described in 2015 by Changhan Lee and Pinchas Cohen's group at the University of Southern California. Muscle appears to be its main target, where it nudges cells toward burning glucose and fat by switching on AMPK, the same energy-sensing enzyme that exercise and metformin activate.
Almost everything known about injected MOTS-c comes from mice. Daily injections stopped high-fat-diet mice from gaining fat and becoming insulin resistant, and in old mice they roughly doubled treadmill running time. In people, the data so far are observational: blood and muscle levels rise during exercise, and an East Asian gene variant that weakens MOTS-c is linked to higher type 2 diabetes risk in sedentary men. No randomized trial of MOTS-c itself has published results. A modified version called CB4211 was tested for four weeks in 20 people with fatty liver; it lowered liver enzymes and glucose but did not beat placebo on liver fat, and the results were announced in a press release, not a journal.
Regulators treat it as an unapproved research compound. WADA named it on the Prohibited List in 2025. The FDA moved it out of its Category 2 'significant safety risks' compounding list in April 2026, and an FDA advisory committee voted 7-5 in July 2026 to recommend adding it to the list pharmacies may compound from, but FDA had not finished that rulemaking as of this review, so it is still not a lawful 503A compounding ingredient. A placebo-controlled Phase 2a trial in adults with prediabetes started in 2026.
What it binds to, and what happens inside the body after that, step by step.
In mouse muscle and cultured cells, MOTS-c slows the folate cycle and the purine-building pathway attached to it. That causes AICAR, an intermediate of purine synthesis, to build up, and AICAR switches on AMPK. Under metabolic stress MOTS-c also moves into the cell nucleus and changes the expression of stress-response and antioxidant genes, partly through NRF2.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
Every effect people cite for MOTS-c injections, including less fat gain, better insulin sensitivity and longer running time, was shown in mice. Human studies only measure the body's own MOTS-c, showing it rises with exercise and is linked to diabetes risk through a gene variant; none give MOTS-c to people and report outcomes in a journal. The one human dosing study was of CB4211, an analog, in 20 patients for four weeks, reported only in a press release.
27,527 people in three cohorts (J-MICC, MEC, TMM), plus mice
Men carrying the m.1382A>C variant, which makes a weaker K14Q form of MOTS-c, had a higher prevalence of type 2 diabetes, mainly if they were inactive; women were unaffected.
Read the study211 Japanese adults for fiber typing; 721 athletes and 873 controls for genotype frequency
Carriers of the K14Q variant had more fast-twitch fibers and the variant was more common in sprint and power athletes (6.5%) than endurance athletes (2.9%).
Read the study49 breast cancer survivors randomized to 16 weeks of exercise or usual care (secondary analysis)
Exercise raised blood MOTS-c in non-Hispanic White women but not in Hispanic women; MOTS-c was the outcome measured, not a treatment.
Read the study65 healthy adults (Phase 1a); 20 adults with obesity and fatty liver, 11 drug and 9 placebo (Phase 1b)
Over 4 weeks, ALT fell 21% versus a 4% rise on placebo and glucose fell 6% versus 0%, but liver fat dropped about equally in both groups (-5.03 vs -4.88 points). Reported by press release; this is an analog, not MOTS-c.
Read the studyMice on a high-fat diet and aged mice; cultured cells
Identified MOTS-c and showed it inhibits the folate cycle, activates AMPK, and prevented diet-induced obesity and insulin resistance in mice.
Read the studyYoung, middle-aged and old mice; plus 10 sedentary young men in an exercise sub-study
Old mice given 15 mg/kg ran about 2-fold longer; in the 10 men a bike session raised muscle MOTS-c 11.9-fold and blood levels about 1.5-fold. Late-life dosing trended toward a 6.4% longer median lifespan (not significant overall).
Read the studyCultured human and mouse cells
Under glucose restriction MOTS-c entered the nucleus in an AMPK-dependent way and regulated antioxidant-response genes with NRF2.
Read the studyThese are questions the published research has not answered.
No product containing MOTS-c is approved as a medicine by the FDA.
Not approved by FDA or any other regulator for any use. WADA added MOTS-c by name to the 2025 Prohibited List under S4.4.1, activators of AMPK, prohibited at all times. A Phase 2a, placebo-controlled trial (NCT07505745, Hudson Biotech) began in February 2026 in adults with prediabetes and overweight; no results yet. CB4211, a modified analog from CohBar, finished a Phase 1a/1b study in 2021 and was not advanced to a larger trial.
No human half-life has been published for MOTS-c, so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.
No human study or approved label has published a dose for MOTS-c, so there is no table to show.
No dose of MOTS-c has been tested in a published human study or approved on a label. Numbers that circulate online come from animal studies scaled up by guesswork or from sellers. We do not reproduce them.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
Exercise raises MOTS-c and injecting it improved running in mice, but no human trial has tested whether injecting it does anything that exercise does.
Mice on a high-fat diet gained less fat. The only human dosing data, from the analog CB4211, showed a weight trend over 4 weeks with no reported numbers.
FDA removed it from Category 2 and an advisory committee recommended it, but it is not on the 503A bulks list or in Category 1, so pharmacies still cannot lawfully compound it until FDA finishes rulemaking.
In the one mouse lifespan test, late-life dosing produced a 6.4% longer median lifespan that was not statistically significant overall. There are no human data.
Consistently shown in mice and supported by human gene data linking a weaker MOTS-c variant to diabetes, but it has not been shown by giving MOTS-c to people.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Discussed online as pairing an AMPK activator with an NNMT inhibitor that raises cellular NAD+ in fat cells.
EvidenceNo study, animal or human, has tested this combination.
Both are called exercise mimetics; one acts through AMPK, the other through ERR nuclear receptors.
EvidenceEach has only mouse data on its own, and the combination has never been studied.
Proposed as adding a muscle-metabolism signal to appetite-driven weight loss.
EvidenceUntested. Semaglutide has large RCTs; MOTS-c has none, so any benefit would be from the GLP-1 drug.
Research suppliers typically list freeze-dried peptide at -20 C, protected from light and moisture. No pharmaceutical stability data are published.
No validated stability data. General peptide practice is refrigeration at 2-8 C and short use windows; potency over time is unknown.
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