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Peptide profile

MOTS-c: FDA Status, Research and Uses

By Living+. Updated October 28, 2026.

Key takeaway

MOTS-c is a 16-amino-acid mitochondrial peptide first described in 2015 [1, 6]. It is not FDA approved or on the 503A bulks list [1, 14]. FDA staff proposed not listing it in July 2026 [3, 4]. Since October 28, 2026, an HHS interim policy covers compounding it under set conditions [14]. Research is mostly in rodents, for obesity and bone loss [1, 6].

At a glance

Where it stands

Checked

  • FDA approvedNoNo approved product
  • Pharmacy compounding (503A)HHS interim policyOn HHS's interim enforcement policy (Appendix A), released Oct 28, 2026. HHS does not intend to take action against a state-licensed pharmacy, federal facility or licensed physician compounding MOTS-c acetate for subcutaneous or intramuscular injection, with a patient-specific prescription and the policy's other conditions (FDA-registered source with a certificate of analysis, single ingredient, adverse event reporting). It is not FDA approval and not a place on the 503A bulks list; HHS may revisit it if a safety or quality problem arises. The July 2026 advisory committee voted in favor of listing it, and FDA's final rule is still pending.
  • Outsourcing facilities (503B)Not nominatedNot on FDA's 503B categories list (updated March 21, 2025).
  • WADA (sport)ProhibitedS4.4.1 Metabolic modulators, AMPK activators (named: MOTS-c)
Same data as the Status Tracker. Checked against 10 sources

Key facts

Class
Mitochondrial-derived peptide [1, 6]
Length
16 amino acids [1, 6]
Half-life
Not established in humans; broken down quickly in human blood in a lab test [1]
Route in studies
Injection into the abdomen (intraperitoneal) in animal studies; no human dosing studies found [1]
First studied
2015 [1, 6]

How it works

MOTS-c is a small peptide made from a short gene inside mitochondria, the energy centers of cells. The gene sits within the mitochondrial 12S rRNA region. Researchers who first described it in 2015 found it in skeletal muscle and in blood in humans and rodents [1, 6].

In mice, MOTS-c acted mainly on skeletal muscle. It blocked the folate cycle in cells, which led to activation of AMPK, an enzyme that senses cell energy [6]. Blocking AMPK removed many of its effects in mice, so AMPK seems to be part of how it acts, though FDA notes its exact targets are unknown [1].

In rodent studies it was tested against diet-induced obesity and insulin resistance [6], weight gain and bone loss after removal of the ovaries [8, 9], and blood vessel calcification in rats [10]. Old mice given it ran better on a treadmill [7].

In people, MOTS-c has only been measured, not given as a treatment in published studies. Exercise raised the body's own MOTS-c in muscle and blood [7], and obese boys had lower blood levels than controls [11]. FDA found no human studies of MOTS-c given as a drug and no human dosing data [1].

What the research shows

1 human trial5 animal studies

  1. 2018Human trial

    Du et al. 2018 (blood levels in children)

    40 children and teens with obesity and 57 controls Case-control study measuring natural MOTS-c blood levels; no MOTS-c was given [11]

    Blood MOTS-c levels were lower in obese boys and were linked with markers of insulin resistance [11].

    Read the study
  2. 2021Animal study

    Reynolds et al. 2021 (exercise and aging)

    Mice; exercise blood and muscle samples from people Mouse treatment studies plus measurement of natural MOTS-c after exercise in humans [7]

    MOTS-c raised physical performance in young, middle-aged and old mice. In humans, exercise raised natural MOTS-c levels [7].

    Read the study
  3. 2020Animal study

    Wei et al. 2020 (vascular calcification)

    Studied for blood vessel calcification and reduced it in this rat model [10]

    Rats Controlled rat study, daily dosing for 4 weeks [10]

    Read the study
  4. 2019Animal study

    Lu et al. 2019 (ovariectomy and weight)

    Studied for menopause-like weight gain

    Mice after ovary removal Controlled mouse study, 12 weeks [1, 8]

    Treated mice gained less weight and had better insulin sensitivity [8].

    Read the study
  5. 2016Animal study

    Ming et al. 2016 (ovariectomy and bone)

    Studied for osteoporosis

    Mice after ovary removal Controlled mouse study, daily dosing for 12 weeks [9]

    Bone loss was smaller on micro-CT scans [9].

    Read the study
  6. 2015Animal study

    Lee et al. 2015 (discovery, Cell Metabolism)

    Studied for metabolism

    Mice and cell culture Discovery study with high-fat diet and aging mouse models [6]

    Treated mice were protected from diet-induced obesity and insulin resistance [1, 6].

    Read the study

Doses used in studies

There are no published human dosing studies of MOTS-c. FDA found no clinical studies or human exposure data for any route [1].

Animal studies gave MOTS-c by injection into the abdomen. Doses included 0.5 mg/kg per day for 8 weeks in high-fat diet mice and 5 mg/kg per day in insulin sensitivity tests [1], 5 mg/kg per day for 12 weeks in mice after ovary removal [9], and 15 mg/kg three times a week in old mice [1]. A rat study used 5 mg/kg per day for 4 weeks [10].

Dosing is set by a licensed provider.

Side effects and safety

MOTS-c is not FDA approved, so there is no FDA label or boxed warning. FDA has not identified any human exposure data for MOTS-c by any route. It says the safety risks in humans are unknown [1, 2].

FDA also says compounded MOTS-c may carry a significant risk of immune reactions and has impurity and quality concerns [2]. FDA found no published animal toxicity studies to inform safety, and a lab study showed it breaks down quickly in human blood [1]. A search of FDA's adverse event database found no reports for MOTS-c [1].

Common questions

Is MOTS-c FDA approved?

No. FDA states MOTS-c is not a component of an FDA-approved drug and has no USP or NF monograph [1].

Is MOTS-c legal to compound?

MOTS-c is still not on the 503A bulks list and is not FDA approved, and FDA's final rule is pending [1, 14]. FDA staff proposed not to list it in July 2026 [3, 4]. Since October 28, 2026, an HHS interim policy says HHS does not intend to take action against state-licensed pharmacies, federal facilities or licensed physicians who compound MOTS-c acetate under set conditions [14]. It covers subcutaneous or intramuscular injectable forms [14]. The policy is not FDA approval, and HHS may revisit it [14].

What happened at the July 2026 FDA meeting on MOTS-c?

FDA advisers discussed MOTS-c for obesity and osteoporosis on July 23, 2026, after FDA staff proposed against listing it [3, 4]. HHS's October 28, 2026 policy states the committee voted in favor [14]. FDA's final rule is still pending [14].

Is MOTS-c banned in sports?

Yes. The WADA Prohibited List names MOTS-c under S4.4.1 metabolic modulators, banned at all times [5].

Has MOTS-c been tested in humans?

FDA found no human studies of MOTS-c given as a drug. Human studies so far only measured the body's own MOTS-c levels [1, 7, 11].

What is MOTS-c studied for?

In mice and rats it was studied for obesity, insulin resistance, bone loss, physical decline with age and blood vessel calcification [6, 7, 8, 9, 10].

Is MOTS-c safe?

Its safety in humans is unknown. FDA has no human exposure data and flags a risk of immune reactions with compounded forms [1, 2].

Does exercise raise MOTS-c?

In a 2021 study, exercise raised natural MOTS-c levels in human muscle and blood [7].

Sources

  1. FDA briefing document: evaluation of MOTS-c-related bulk drug substances, PCAC July 23-24, 2026
  2. FDA: Certain bulk drug substances for use in compounding that may present significant safety risks
  3. FDA: July 23-24, 2026 meeting of the Pharmacy Compounding Advisory Committee
  4. FDA briefing document introduction, PCAC July 23-24, 2026
  5. WADA: 2026 Prohibited List (PDF)
  6. Lee et al. 2015, Cell Metab (PubMed)
  7. Reynolds et al. 2021, Nat Commun (PubMed)
  8. Lu et al. 2019, J Mol Med (PubMed)
  9. Ming et al. 2016, Biochem Biophys Res Commun (PubMed)
  10. Wei et al. 2020, Cardiorenal Med (PubMed)
  11. Du et al. 2018, Pediatr Diabetes (PubMed)
  12. WADA: Prohibited List resource page (2026 List in force)
  13. Federal Register: PCAC notice of meeting, published April 16, 2026
  14. HHS: Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances (Oct 28, 2026)
  15. Federal Register: HHS notice of availability, FR Doc. 2026-22192 (publishes Oct 30, 2026)

Updated October 28, 2026. Educational information, not medical advice.