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PeptideMostly animalNot FDA approved

MOTS-c

Mitochondrial open reading frame of the 12S rRNA-c

Last reviewed October 27, 2026 · 10 sources · Written for general readers · Compare with another compound →

The bottom line

MOTS-c is a small peptide coded by DNA inside mitochondria, and in mice it curbed weight gain, improved insulin response and boosted running. FDA found no human clinical studies, no human safety data and quality problems with the material sold, and it recommended against compounding it. An FDA advisory panel still voted 7 to 5 in July 2026 to allow compounding, but that vote is not binding and MOTS-c is not FDA approved.

Where the evidence stands

What it is

MOTS-c is a peptide 16 amino acids long. Unusually, it is coded by DNA inside mitochondria, the cell’s power plants, rather than the main DNA in the cell nucleus. It was first described in 2015.[1][2]

The body makes small amounts on its own, and exercise raises them.[3] Lab made MOTS-c is sold online and through some clinics as an injection for weight loss, blood sugar control, endurance and aging. FDA found it is not well characterized: key data on impurities, clumping and bacterial contamination were missing.[1]

Name
MOTS-c (Mitochondrial open reading frame of the 12S rRNA-c)
Other names
MOTS c, mitochondria derived peptide MOTS-c
Type
Peptide
Sequence
MRWQEMGYIFYPRKLR
CAS number
1627580-64-6
Formula
C101H152N28O22S2
Molecular weight
About 2174.6 g/mol

How it works

Researchers think MOTS-c acts mainly in muscle to change how cells handle fuel.

  • Studies in cells and mice suggest MOTS-c works mainly in muscle and switches on AMPK, a cell energy sensor that helps the body use sugar and fat.[2]
  • FDA noted that no clear molecular target or dose response has been shown.[1]
  • A lab study found MOTS-c is quickly broken into fragments in human blood, raising doubts that injected peptide stays active long enough to matter.[1]

The mechanism comes from mouse and lab work and has not been confirmed in people.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Metabolic and fitness benefits in mice

  • In the 2015 discovery study, MOTS-c prevented diet induced obesity and insulin resistance in mice, along with age related insulin resistance.[2]
  • Mice on a high fat diet given MOTS-c gained less weight than untreated mice and responded better to insulin.[1]
  • MOTS-c improved physical performance in mice aged 2, 12 and 22 months, and treatment started very late in life increased physical capacity and healthspan.[3]
  • Late life treatment raised median mouse lifespan from 912 to 970 days.[1]
  • Other rodent and cell studies reported effects on bone cells and blood vessel calcium buildup. Most gave the peptide by injection into the belly cavity.[1]

Limit: No standard toxicity, cancer or reproductive studies exist, and FDA noted the animal studies lacked dose response testing.[1]

Human studies

No human trials

  • No published study has given MOTS-c to people. FDA’s 2026 review found no clinical studies, no pharmacokinetic data (how the body absorbs and clears it) and no human exposure data, and its adverse event database held no reports.[1]
  • The only human tissue test was in a dish: MOTS-c mixed with human blood was quickly cut into shorter fragments within an hour.[1]
  • Studies of the body’s own MOTS-c show that exercise raises its levels in human muscle and blood. This describes natural MOTS-c, not taking it.[3]

Limit: With no human studies, its safety and any benefit in people are unknown.[5]

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Burns fat and helps weight loss

Only in animals

In mice fed a high fat diet, MOTS-c injections prevented much of the weight gain seen in untreated mice.[1][2] No study has tested weight loss in people.[1]

Improves blood sugar and insulin

Only in animals

Treated mice needed about 30 percent more sugar infused to keep blood sugar steady during a clamp test, a sign their bodies responded better to insulin, and insulin response in aged muscle moved back toward young levels.[1] These results come only from mice, and no human data exist.[1]

Boosts endurance and exercise performance

Only in animals

MOTS-c improved running performance in young, middle aged and old mice.[3] In people, exercise raises the body’s own MOTS-c in muscle and blood, but no study has given MOTS-c to people to see if it improves fitness.[3][1]

Slows aging and extends life

Only in animals

In mice treated starting late in life, median lifespan rose from 912 to 970 days and maximum lifespan from 1047 to 1120 days, and physical ability improved.[1][3] A gene variant in the MOTS-c region, common in Northeast Asian people, has been proposed as one possible factor in Japanese longevity, but this is a hypothesis, not a test of the peptide.[4]

Strengthens bones and protects blood vessels

Only in animals

MOTS-c raised bone forming markers in rat stem cells in a dish and reduced bone loss in a mouse model. In a rat model it reduced calcium buildup in the aorta.[1] None of this has been studied in people.

Known risks and side effects

  • Unknown safety. FDA says safety risks in humans are unknown because no human studies or standard toxicity studies exist.[1]
  • Immune reactions. FDA is concerned that clumped peptide and impurities could trigger immune reactions, especially with injection under the skin.[1]
  • May not stay active. MOTS-c breaks down fast in human blood in the lab, so it is unknown whether an injection reaches levels that do anything.[1]
  • Unregulated products. MOTS-c is sold online, sometimes mixed with other substances, and FDA found the material poorly characterized, with missing tests for impurities and bacterial toxins. What is in a vial is not assured.[1]
  • Banned in sport. WADA lists MOTS-c as a prohibited metabolic modulator at all times.[6][5]

Regulatory status

Today: MOTS-c is not FDA approved. FDA removed it from Category 2 in April 2026,[7] and it is not on FDA’s current nomination list in any category.[8] An FDA panel voted in July 2026 to allow compounding, but FDA must decide and then go through formal rulemaking first.[9]

  1. Scientists first describe MOTS-c and its metabolic effects in mice.[2]
  2. A study reports that MOTS-c improves physical performance in mice of all ages and that exercise raises natural MOTS-c in people.[3]
  3. FDA announces it will remove MOTS-c and 11 other peptides from Category 2 after nominations were withdrawn.[7]
  4. FDA’s briefing finds no human studies and proposes not adding MOTS-c to the compounding list.[1]
  5. FDA’s Pharmacy Compounding Advisory Committee meets on MOTS-c and six other peptides.[10]
  6. The panel votes 7 to 5, with 2 abstaining, to recommend allowing compounding. The vote is not binding.[9]

Sources

  1. U.S. Food and Drug Administration. Evaluation of MOTS-c-related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate) for Inclusion on the 503A Bulk Drug Substances List. Briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026 (memo dated May 11, 2026). FDA
  2. 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. PMID 25738459
  3. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1). PMID 33473109
  4. Fuku N, Pareja-Galeano H, Zempo H, et al. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? Aging Cell. 2015;14(6):921-923. PMID 26289118
  5. U.S. Anti-Doping Agency. What is the MOTS-c peptide? USADA
  6. World Anti-Doping Agency. The Prohibited List (2026 List, in force from January 1, 2026). WADA
  7. Frier Levitt. FDA to Remove 12 Popular Peptides from the Category 2 “Do Not Compound” List. April 2026. Legal news
  8. U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act. Updated May 14, 2026. FDA
  9. AJMC. FDA Panel Backs 6 Peptides for Compounding. July 31, 2026. Trade news
  10. U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee meeting agenda, July 23-24, 2026. FDA
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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