MOTS-c: research, side effects and dosage in studies
In short
MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome whose treatment effects are known only from mice and cells [1]C. There are no published studies giving it to humans, and it has no marketing authorisation [6, 9]regulator.
- In mice MOTS-c prevented diet-induced weight gain and insulin resistance [1]C and improved physical performance in old mice [2]C. The results apply to mice.
- In humans only the body's own MOTS-c has been measured around exercise [2]B [3]A. The FDA found no data showing that it has been given to humans [6]regulator.
- In a study on human cells, MOTS-c reduced cell proliferation and increased the expression of genes linked to inflammation [4]D.
- WADA prohibits MOTS-c at all times (class S4.4) [7]regulator, and Fimea warns against injectable peptides bought online [8]regulator.
What is MOTS-c?
MOTS-c is a 16-amino-acid peptide encoded in the mitochondria's own genome. Mitochondria are the energy producers of cells, and they have a small genome of their own. In 2015 researchers described a short reading frame in the mitochondrial 12S rRNA gene that encodes this peptide, and named it MOTS-c [1]C.
Online, MOTS-c is sold as a research chemical. According to Fimea, a "for research use only" label means the product is not intended for humans [8]regulator. Basics: What are peptides?. All substances: Peptides A-Z.
Evidence at a glance
Each cell gives the kind of study and its source. The letter is the evidence level, not the result.
| Claimed effect | Humans | Animals | Cells |
|---|---|---|---|
| Insulin resistance and weight gain | No treatment study [6]regulator | In mice prevented insulin resistance and weight gain caused by ageing and a high-fat diet [1]C | Activated AMPK [1]D |
| Physical performance | No treatment study [6]regulator | Improved performance in young, middle-aged and old mice [2]C | - |
| Own MOTS-c and exercise | Exercise increased own MOTS-c in muscle and blood [2]B; rise after endurance exercise not statistically certain [3]A | - | - |
| Tissue repair | - | Cells pre-treated with MOTS-c did not improve kidney outcomes in a mouse model [4]C | Reduced proliferation of fat-tissue stem cells [4]D |
| Safety | No human exposure data [6]regulator | - | Increased expression of genes linked to ageing and inflammation [4]D |
"-" = no such study is known.
What is MOTS-c studied for?
MOTS-c is studied for metabolism and exercise. No use is approved, and treatment effects have not been studied in humans [6]regulator [9]regulator.
- Metabolism and weight gain: mouse studies [1]C, see Promising, but only in animal and cell studies.
- Performance and ageing: mouse studies [2]C.
- Effect of exercise on own MOTS-c: levels measured in humans [2]B [3]A [5].
Claims online. Claims about weight loss and better endurance are based on mouse studies [1, 2]C. This has not been studied in humans [6]regulator.
How does MOTS-c work?
In mouse and cell studies the main target of MOTS-c appeared to be skeletal muscle. Inside the cell it inhibited the folate cycle and the linked production of purines, which led to activation of the enzyme AMPK. AMPK is a regulator that senses the cell's energy state [1]C.
The mechanism has not been studied in humans, because the substance has not been given to humans in published studies [6]regulator.
Has MOTS-c been studied in humans?
Not as a treatment: the FDA has not identified any data showing that products containing MOTS-c have been given to humans by any route [6]regulator. In humans only the body's own MOTS-c has been measured [3]A [5].
Human studies
- Exercise and own MOTS-c (2021). In humans exercise increased the body's own MOTS-c in muscle and blood [2]B.
- Endurance and resistance exercise (2021). 30 people were randomised to endurance exercise (45 minutes of cycling), resistance exercise or a control group. Blood MOTS-c showed a trend to rise after endurance exercise, but the change was not statistically certain. Levels were not related to fitness or leg strength [3]A.
- Review (2026). A systematic review found nine studies on exercise and mitochondria-derived peptides. Most reported a trend towards higher levels after exercise, but the studies were few and their designs varied [5]. The review concerns the body's own levels and does not describe human studies giving MOTS-c [5].
Promising, but only in animal and cell studies
These findings look good, but they have not been tested in humans [6]regulator. Results from animal and cell studies cannot be transferred to humans, and they say nothing about the effects of a product sold online, because its content may differ from the label [8]regulator.
-
Insulin resistance and weight gain no human studies
In the first MOTS-c study, MOTS-c given to mice prevented insulin resistance caused by ageing and by a high-fat diet, as well as diet-induced weight gain [1]C.
If it held in humans: it could help prevent type 2 diabetes and obesity.
Why it might not translate: the results come from mice and have not been reproduced in human treatment trials [1]C [6]regulator. In fat-tissue stem cells from people with obesity, MOTS-c reduced proliferation and increased the expression of genes linked to ageing and inflammation [4]D.
Evidence now: mouse and cell studies [1]C. No treatment study in humans [6]regulator.
-
Performance with ageing no human studies
In a study published in 2021, MOTS-c improved physical performance in young (2 months), middle-aged (12 months) and old (22 months) mice. Intermittent treatment started in very old mice (23.5 months) increased physical capacity [2]C.
If it held in humans: the decline in physical function in older people could be slowed.
Why it might not translate: the result comes from one mouse study [2]C, and in humans the level of the body's own MOTS-c was not related to fitness or leg strength [3]A.
Evidence now: one mouse study [2]. No treatment study in humans [6]regulator.
Who studies MOTS-c?
The studies covered on this page are basic research: mouse and cell experiments by the group that described MOTS-c [1]C, a mouse performance study [2]C, a human exercise study of the body's own levels [3]A and a stem cell study [4]D.
MOTS-c itself has not been given to humans in published studies [6]regulator. The US company CohBar developed a modified peptide, CB4211, from MOTS-c [10]E, not peer-reviewed, and it was tested in a phase 1a/1b study in healthy people and people with fatty liver disease in 2018-2021 [12]E, not peer-reviewed. According to the company, in the four-week part of the study 23 obese people with fatty liver disease received CB4211 or placebo. There were no serious adverse events, but injection site reactions occurred in 79% of those given CB4211 and 33% of those given placebo [11]E, not peer-reviewed. The results have not been published in a peer-reviewed journal. CB4211 is not the same substance as the MOTS-c sold online.
Who wrote this page: the editorial team
This page was written by the Molecular Recovery editorial team. The draft was made with the help of AI, and the claims were checked against the sources (AI policy). The page has not been medically reviewed. How we work: About us.
What are the side effects of MOTS-c?
The side effects of MOTS-c are not known. The harms of giving MOTS-c have not been studied in humans, and the FDA states it is not known whether the substance would cause harm in humans [6]regulator.
What users report. In the Reddit accounts we compiled (not research), 43 of 76 people (57%) reported some harm, most often: injection site pain or reaction (14, 18%), allergic reaction, hives or rash (7, 9%) and fatigue (6, 8%). People tend to post when something goes wrong, so this share does not tell how common harms are. In all, 43 people described how strong a harm was, and 5 of them described it as severe. The harms in detail: MOTS-c user experiences.
Risks in products
According to the FDA, preparations containing MOTS-c may pose a significant risk of immune reactions for certain routes of administration, and there may be problems with peptide impurities and characterising the active substance [6]regulator.
According to Fimea, the harms and long-term effects of injectable products bought online may be unknown, and impurities such as endotoxins can cause serious harm [8]regulator.
Findings in cell studies
In stem cells isolated from the fat tissue of people with obesity, added MOTS-c increased the expression of genes linked to cell ageing and inflammation [4]D. A cell study does not tell what would happen in a human. More: Side effects and safety.
Interactions and who lacks data
Because there are no human exposure data [6]regulator, nothing is known about interactions with other medicines in humans. For the same reason there are no data for pregnancy, breastfeeding, children or people with long-term illnesses.
What speaks against it and what is unknown
Not all results are favourable, and in humans there are only level measurements [3]A [4]D.
Contrary evidence
- In fat-tissue stem cells from people with obesity (6 donors per group), MOTS-c activated AMPK but reduced cell proliferation. In a mouse model, cells pre-treated with MOTS-c did not improve kidney outcomes [4]C.
- In humans, blood MOTS-c was not related to fitness or leg strength, and the rise after endurance exercise was not statistically certain [3]A.
What the evidence does not support
- "MOTS-c causes weight loss in humans": the result comes from mice [1]C; this has not been studied in humans [6]regulator.
- "MOTS-c is exercise in a vial": in humans only the effect of exercise on the body's own MOTS-c has been measured [2]B [3]A, not giving the substance.
- "There are human studies of MOTS-c": the FDA found no human exposure data [6]regulator.
- "The vial contains what the label says": according to Fimea, a product may contain a different substance than the label says [8]regulator.
MOTS-c dosage in studies
There is no dose studied in humans, because the FDA found no human exposure data at all [6]regulator. The table shows, as an example, the dose and frequency used in a mouse study. It is not a recommendation, and an animal dose does not transfer to humans.
| Study | Who | Dose and route | Duration |
|---|---|---|---|
| Performance with ageing (2021) | very old mice | 15 mg/kg into the abdominal cavity three times a week (mouse dose) | intermittent treatment [2]C |
There are no doses studied in humans, so there is no dose page, and no calculator page opens with MOTS-c preselected. The general calculator's list includes MOTS-c only to fill in a vial size. Doses of other substances: Dosing.
Situation in the United States
In the United States, MOTS-c has been among the FDA category 2 substances, meaning substances nominated for pharmacy compounding that may present significant safety risks. The nomination was later withdrawn by the nominator. The FDA risk assessment is still on the page (updated 22 Apr 2026) [6]regulator.
Is MOTS-c legal in Finland?
MOTS-c has no marketing authorisation as a medicine in the EU [9]regulator, and Fimea warns against injectable peptides bought online [8]regulator.
- Marketing authorisation. The EMA data on centrally authorised medicines (15 Sep 2026) contain no product with MOTS-c [9]regulator.
- Fimea warning, 29 June 2026. A product injected through the skin may be a medicine in Finland, and a "for research use only" label means the product is not intended for humans. Fimea advises buying medicines only from legal pharmacies [8]regulator.
- Import. Ordering medicines from outside the EU is covered on Peptides and the law in Finland. Bringing them back from travel: Travelling with peptides.
This is not legal advice. Disclaimer.
Is MOTS-c doping?
Yes. MOTS-c is named on the WADA 2026 Prohibited List in class S4.4 (metabolic modulators), among activators of AMPK. Substances in class S4 are prohibited at all times, both in and out of competition [7]regulator.
How is a MOTS-c product assessed?
You cannot be sure what a product contains. According to Fimea, there is no reliable information on the content, quality and safety of products sold as research chemicals, and a product may contain a different substance than the label says [8]regulator. The FDA highlights peptide-related impurities and difficulty characterising the active substance [6]regulator.
A seller's own certificate of analysis (COA) does not by itself show that a product is pure, sterile or free of endotoxin. For injectables, Fimea names endotoxins as a particular risk [8]regulator. More: How to read a COA and check a test result. Handling: Mixing and handling.
FAQ
What is MOTS-c?
A 16-amino-acid peptide encoded in the mitochondrial genome, described in 2015 [1]C.
Has MOTS-c been studied in humans?
Not as a treatment. In humans researchers have mainly measured the body's own MOTS-c around exercise [2]B [3]A. Giving it to humans has not been published, and the FDA found no human exposure data [6]regulator. CB4211, a peptide modified from MOTS-c, has been given to humans in a company study whose results have not been published in a peer-reviewed journal [10, 11]E, not peer-reviewed.
Does MOTS-c cause weight loss?
This is not known. In mice it prevented diet-induced weight gain [1]C. This has not been studied in humans [6]regulator.
What are the side effects of MOTS-c?
This is not known, because harms have not been studied in humans. According to the FDA, preparations may carry a risk of immune reactions [6]regulator, and in a cell study MOTS-c increased the expression of genes linked to inflammation [4]D.
MOTS-c dosage: is there a dose studied in humans?
No [6]regulator. The page shows a mouse study dose as an example: MOTS-c dosage in studies. It does not transfer to humans and is not a recommendation [2]C.
Is MOTS-c a banned substance in sport?
Yes. It is named on the WADA Prohibited List in class S4.4, which is prohibited at all times [7]regulator.
Is MOTS-c an approved medicine?
No. The EMA data contain no medicine with MOTS-c [9]regulator.
Is MOTS-c bought online safe?
This is not known. Fimea warns against injectable peptides bought online [8]regulator, and the FDA says safety information is lacking [6]regulator.
What do users themselves report about MOTS-c?
In the Reddit accounts of 76 people we compiled (not research), 37 (49%) reported some benefit and 43 (57%) some harm. The accounts are self-selected and prove neither that it works nor that it is safe: MOTS-c user experiences.
Read the research yourself: sources
Every source opens the original publication or the regulator's page. The level shows what the source itself reports.
- 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;21:443-54. PMID 25738459 C
- 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;12:470. PMID 33473109 C
- von Walden F, Fernandez-Gonzalo R, Norrbom J, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol. 2021;131:1035-1042. PMID 34351816 A
- Xing L, Lu B, Zhu X, et al. Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells. Inflamm Regen. 2026;46. PMID 42324588 D
- Ayubi N, Wibawa JC, Kurnaz M, et al. Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review. Physiol Int. 2026. PMID 42640735 (review)
- U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 22 Apr 2026). FDA regulator
- World Anti-Doping Agency. The 2026 Prohibited List, class S4.4 Metabolic modulators (in effect from 1 Jan 2026). WADA regulator
- Fimea. Fimea varoittaa: älä käytä verkosta ostettuja pistettäviä peptidejä / Fimea warns: do not use injectable peptides purchased online. 29 Jun 2026. Fimea regulator
- European Medicines Agency. Medicine data (centrally authorised medicines, data set of 15 Sep 2026): no product with MOTS-c as active substance. EMA regulator
- CohBar, Inc. Annual report (Form 10-K) for 2020, filed 30 Mar 2021: CB4211 described as "a novel, enhanced analog of MOTS-c". sec.gov E, not peer-reviewed
- CohBar, Inc. Investor presentation with Phase 1a/1b topline results of CB4211, 10 Aug 2021 (Form 8-K, exhibit 99.3): Phase 1b 23 obese subjects with NAFLD randomised 1:1, 25 mg once daily under the skin for 4 weeks; injection site reactions 79% vs 33% with placebo; no serious adverse events. sec.gov E, not peer-reviewed
- ClinicalTrials.gov. NCT03998514: A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease (CohBar; phase 1; completed 19 Apr 2021; 88 participants; no results posted as of 13 Oct 2026). ClinicalTrials.gov E, not peer-reviewed
Research sources checked 9-13 Oct 2026. Regulator and registry sources checked 15 Sep to 13 Oct 2026.
Evidence levels: A = randomised human trial or meta-analysis · B = observational human study or case series · C = animal study · D = cell or laboratory study · E = not peer-reviewed · regulator = a regulator's assessment or decision, not research evidence. The marker official means official product information (summary of product characteristics or label); it is not research evidence. For a review, the level shows what kind of research the statement rests on. No level: statements that something has not been studied, reviews' interpretations, named hypotheses and the general rules in our certificate-of-analysis guide.
Content is general information about research, not medical advice. If you have symptoms, contact a healthcare professional.