Underground Biohacking
Metabolic

MOTS-c

Chris Hallewell, founder of Underground Biohacking

By , Founder, Underground Biohacking

Last reviewed

Research use only. Not FDA-approved.

MOTS-c is a peptide your own mitochondria make. Research groups use it to study insulin sensitivity, exercise capacity and ageing. Nearly all of that work is in mice and in cells. The one finding measured directly in people is that exercise raises your own MOTS-c. No trial has yet reported what happens when you inject it, so there is no clinically established dose and no human safety record.

What is MOTS-c?

MOTS-c is a short peptide, 16 amino acids long. Your mitochondria make it themselves. Mitochondria are the parts of your cells that turn food into usable energy. They also carry their own small loop of DNA, separate from the DNA in the cell nucleus. MOTS-c is written in that mitochondrial DNA, inside a gene called 12S rRNA. The name is short for mitochondrial open reading frame of the 12S rRNA type-c. A team at the University of Southern California described it in 2015. That makes it a mitochondrial-derived peptide, a small family that also includes humanin. These peptides act as signals. They tell the rest of the cell, and the rest of the body, how the mitochondria are coping. MOTS-c turns up in blood, and levels fall as people get older. Exercise pushes them back up.

What is MOTS-c used for?

  • Exercise raises the MOTS-c your own body makes. Researchers measured that rise in human skeletal muscle and in blood.[2]Human study
  • Across three population studies covering 27,527 adults, men carrying a gene variant that weakens MOTS-c had more type 2 diabetes. In one of the three, only the least active men showed the effect.[4]Human study
  • In mice, MOTS-c injections improved insulin sensitivity and stopped a high-fat diet causing obesity. Skeletal muscle is the main target tissue, and the peptide works there by switching on an energy sensor called AMPK.[1]Animal or lab study only
  • MOTS-c injections improved physical performance in young, middle-aged and old mice. Starting the injections late in life still raised their exercise capacity.[2]Animal or lab study only
  • When fuel runs short, MOTS-c moves into the cell nucleus. There it switches on genes that defend the cell against stress.[3]Animal or lab study only
  • MOTS-c switched on heat-producing brown fat in mice and helped them handle cold.[5]Animal or lab study only
  • MOTS-c lowered blood sugar and improved the insulin response in a mouse model of pregnancy diabetes.[6]Animal or lab study only
MOTS-c dosage chart
Typical dose5-10mg per injection, 2-3 times per week
Cycle length8-12 weeks on, 4-8 weeks off
FormInjectable (subcutaneous or intramuscular)

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How does MOTS-c work?

A 16-amino-acid mitochondrial-derived peptide. Activates AMPK signalling, improves insulin sensitivity, and enhances metabolic flexibility. Endogenous expression rises with exercise; declines with age.

How much MOTS-c should you take?

5-10mg per injection, 2-3 times per week

How long should you run MOTS-c?

8-12 weeks on, 4-8 weeks off

How is MOTS-c supplied?

Injectable (subcutaneous or intramuscular)

What are the side effects of MOTS-c?

EffectHow seriousWhat to watch
No human side-effect record exists. Every published result is from cells, mice or rats. The first trial to give MOTS-c to people is still running and has reported nothing.[8]UnknownTreat every dose as untested in people.
Low blood sugar is the effect to watch first. MOTS-c lowers glucose and improves the insulin response in animals, and nobody has dose-tested that in people.[1]Unknown in humansFasting glucose and HbA1c
The effect may differ by sex. In mice, MOTS-c cut weight and improved glucose tolerance in males but did nothing in females.[4]Unknown relevance to peopleNone established

Is MOTS-c legal in 2026?

The FDA has not approved MOTS-c for any use. It sits on an FDA list of substances that were put forward for compounding pharmacies and then withdrawn by whoever nominated them. On that page the FDA states two things. It has found no human exposure data for MOTS-c by any route. And the peptide may carry a real risk of immune reactions by some routes, meaning your immune system could attack the peptide itself. The first study to give MOTS-c to people began in February 2026. It is a 120-person Phase 2a trial in adults with prediabetes and excess weight, registered as NCT07505745. It has reported nothing yet, and its safety follow-up runs into 2027.

Status checked against the primary source.

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Frequently Asked Questions

How much MOTS-c should you take per day?
MOTS-c is not a daily peptide, and there is no clinically established dose. The research-use figure most often quoted is 5 to 10mg per injection, two or three times a week. That number comes from user practice, not from a trial. The first human dosing study only began in 2026 and has not reported.
How long is a MOTS-c cycle?
The common research-use pattern is 8 to 12 weeks on, then 4 to 8 weeks off. No study has tested that schedule. The Phase 2a human trial now running uses 12 weeks of continuous dosing, then a 4-week safety follow-up.
Is MOTS-c FDA approved?
No. The FDA has not approved MOTS-c for any use. On its own compounding pages the FDA states it has found no human exposure data for MOTS-c by any route of administration.
Does MOTS-c work if you already exercise?
Nobody knows. Exercise raises the MOTS-c your body makes on its own. In mice, injected MOTS-c raised exercise capacity without any training. Reviewers describe exercise and injected MOTS-c as sharing some pathways and differing on others. The combination has never been tested in people.
What are the side effects of MOTS-c?
There is no human side-effect record, because no trial has reported one. The Phase 2a study now running is collecting exactly that data and does not finish until 2027. In animals the clearest measured effect is lower blood sugar, so that is the first thing to watch.
Does MOTS-c help you lose weight?
In mice it did. MOTS-c stopped a high-fat diet causing obesity, and it switched on heat-producing brown fat. No human weight result has been published. The trial now running lists body weight among the measures it is tracking.

References

  1. 1.Lee C, Zeng J, Drew BG, et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. PMID: 25738459. DOI: 10.1016/j.cmet.2015.02.009.
  2. 2.Reynolds JC, Lai RW, Woodhead JST, et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. PMID: 33473109. DOI: 10.1038/s41467-020-20790-0.
  3. 3.Kim KH, Son JM, Benayoun BA, Lee C. (2018). The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metabolism. PMID: 29983246. DOI: 10.1016/j.cmet.2018.06.008.
  4. 4.Zempo H, Kim SJ, Fuku N, et al. (2021). A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging. PMID: 33468709. DOI: 10.18632/aging.202529.
  5. 5.Lu H, Tang S, Xue C, et al. (2019). Mitochondrial-derived peptide MOTS-c increases adipose thermogenic activation to promote cold adaptation. International Journal of Molecular Sciences. PMID: 31109005. DOI: 10.3390/ijms20102456.
  6. 6.Yin Y, Pan Y, He J, et al. (2021). The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. Pharmacological Research. PMID: 34798268. DOI: 10.1016/j.phrs.2021.105987.
  7. 7.Woodhead JST, Merry TL. (2021). Mitochondrial-derived peptides and exercise. Biochimica et Biophysica Acta - General Subjects. PMID: 34520826. DOI: 10.1016/j.bbagen.2021.130011.
  8. 8.Zheng Y, Wei Z, Wang T. (2023). MOTS-c: a promising mitochondrial-derived peptide for therapeutic exploitation. Frontiers in Endocrinology. PMID: 36761202. DOI: 10.3389/fendo.2023.1120533.
  9. 9.Mohtashami Z, Singh MK, Salimiaghdam N, et al. (2022). MOTS-c, the most recent mitochondrial derived peptide in human aging and age-related diseases. International Journal of Molecular Sciences. PMID: 36233287. DOI: 10.3390/ijms231911991.
  10. 10.Lee C, Kim KH, Cohen P. (2016). MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radical Biology and Medicine. PMID: 27216708. DOI: 10.1016/j.freeradbiomed.2016.05.015.

This content is for educational purposes only. These compounds are intended for research use. Nothing here is medical advice.