Need help or have questions about your order? Call 510-991-8265Questions about your order? Call 510-991-8265

Sign InShop GLPs
Shop GLPs

MOTS-c Appetite & Cravings Changes: What the Evidence Actually Shows

By
Published Updated Last reviewed
11 linked public sourcesEditorial, sourcing, and corrections policy

At a glance

  • Human appetite data / No study found giving MOTS-c to a person [1]
  • Closest human data / Exercise raises the body's own MOTS-c a little; nobody was injected [3][4]
  • Animal findings / Less diet-induced weight gain and better insulin sensitivity in mice [1][2]
  • Dose for appetite / None established; no human dosing study [1]
  • Approval status / Not FDA-approved; absent from FDA compounding lists [1][5][6][7]
  • Sport / WADA prohibits it at all times under S4.4.1 [8]

What do the mouse studies show?

The 2015 Cell Metabolism paper that named the peptide described a 16-amino-acid sequence encoded in mitochondrial 12S rRNA. In mice, MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance as well as diet-induced obesity; skeletal muscle appeared to be the main target, with AMPK activation [2].

In later experiments, mice on a high-fat diet given 0.5 mg/kg/day intraperitoneally had about 20% lower body weight after 8 weeks, with improved insulin sensitivity [1].

What did the human studies measure?

Reynolds and colleagues reported in Nature Communications that exercise induces the body's own MOTS-c expression in human skeletal muscle and circulation; participants were not given the peptide [3]. One trial of 30 healthy adults randomized to endurance exercise, resistance exercise or control (n=10 each) found humanin rose after endurance exercise; MOTS-c showed only a trend to increase, and plasma levels were not related to fitness [4].

Does the hypothalamic AMPK story support an appetite effect?

AMPK is involved in appetite control in the brain. A 2004 Nature study found that reducing AMPK activity in the hypothalamus lowered food intake and body weight, while constitutively active AMPK raised both [9]. That study did not test MOTS-c. The AMPK activation reported for MOTS-c was in skeletal muscle, and FDA says the peptide's molecular targets are unknown [1][2].

Is there a dose for appetite?

There is no approved dose. The products nominated to FDA were 5 mg and 10 mg subcutaneous injections [1]. Rodent doses of 0.5 to 15 mg/kg cannot be converted into human doses, and FDA found no pharmacokinetic data in humans or live animals [1]. In human blood in vitro the peptide breaks down quickly [1].

Safety and legal status

FDA found no human exposure data by any route and no animal toxicity studies, and its stated concern for injected peptides is immunogenicity from aggregation and peptide-related impurities [1]. MOTS-c is not FDA-approved and appears in none of the three categories on FDA's list for state-licensed pharmacies and physicians or on its list for outsourcing facilities [1][5][6][7].

FDA staff recommended against adding MOTS-c to the pharmacy bulks list. On July 23, 2026 FDA's Pharmacy Compounding Advisory Committee voted in favor of adding it; that vote is non-binding advice, and MOTS-c is not on the list [1][10]. A draft HHS policy filed October 28, 2026 names MOTS-c among six peptides and says HHS does not intend to take enforcement action against certain pharmacies and physicians that compound the acetate form for injection if set conditions are met. The notice says it is not binding, and it is not an FDA approval [11].

Frequently asked questions

Does MOTS-c reduce appetite or cravings in people?
That is unknown. FDA found no study that gave MOTS-c to a person, so hunger, food intake and craving scores have not been recorded after the peptide [1].
Do the mouse weight-loss results apply to humans?
They cannot be assumed to. The mouse doses cannot be converted into human doses, and there is no human dosing or pharmacokinetic study [1].
Is MOTS-c approved or available from a compounding pharmacy?
It is not FDA-approved and not a component of any approved drug [1]. It appears in none of the three categories on FDA's list for state-licensed pharmacies and physicians or on its list for outsourcing facilities [5][6][7]. An advisory committee vote in favor of listing it is non-binding, and a draft HHS enforcement-discretion policy is not an approval [10][11].
Is MOTS-c safe?
That is not known. FDA found no human exposure data by any route and no animal toxicity studies, and its stated concern for injection is immunogenicity from aggregation and peptide-related impurities [1].

References

  1. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  2. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-54. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
  3. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
  4. von Walden F, Fernandez-Gonzalo R, Norrbom J, Emanuelsson EB, Figueiredo VC, Gidlund EK, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985). 2021;131(3):1035-1042. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans
  5. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  6. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  7. Bulk Drug Substances Used in Compounding of the FD&C Act | FDA. Bulk Drug Substances Used in Compounding of the FD&C Act | FDA
  8. World Anti-Doping Agency. World Anti-Doping Agency
  9. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004;428(6982):569-74. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
  10. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee - 07/23/2026 | FDA
  11. U.S. Department of Health and Human Services. Draft enforcement-discretion policy for compounding with certain peptides, Federal Register document 2026-22192. public-inspection.federalregister.gov/2026-22192.pdf
Evidence overview for MOTS-c Appetite & Cravings Changes: What the Evidence Actually Shows