MOTS-c Peptide: Evidence, Risks and Legal Status (2026)

Quick answers

What is it?: A chain of 16 amino acids the body makes, coded in the DNA of mitochondria, the cell’s power plants¹¹⁰. Scientists first described it in 2015¹. Websites sell it for weight loss, blood sugar control, fitness and slower aging³.
Does it work?: Not shown in people. FDA found no published study that gave it to humans³. In mice, injections cut weight gain on a high-fat diet and improved running¹². Longer life in old mice was not proven².
Is it safe?: Unknown. FDA found no safety data in people and no animal safety tests³. FDA also warns that impurities and clumping could trigger unwanted immune reactions³²⁰.
Is it legal?: Not approved, and US pharmacies may not make it³⁵. FDA’s advisers voted 7-5 in July 2026 to allow it, against staff advice, the FDA Law Blog reported³⁶. As of 8 October 2026, FDA had not changed its compounding lists⁵¹⁸. Banned in sport⁷⁸.
What is in the vials?: Most tested samples failed. Of 77 online samples Finnrick tested from February to September 2026, 52 failed its purity-and-dose standard⁹. FDA found no public tests of the raw ingredient for impurities or bacterial toxins³.

What it is

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a chain of 16 amino acids. Its code sits inside MT-RNR1, a gene in mitochondrial DNA, the small separate genome of the mitochondria that power our cells¹¹⁰. It belongs to a family called mitochondrial-derived peptides; humanin was the first one reported¹. Antibody-based tests detect it in human blood and muscle¹², but an anti-doping lab using mass spectrometry could not confirm the blood levels one such test reported¹¹. In cell and mouse studies it acts mainly on skeletal muscle. It slows the folate cycle, a pathway cells use to make DNA building blocks. That lets a molecule called AICAR build up and switch on AMPK, an enzyme that senses the cell’s energy supply¹. Under metabolic stress, MOTS-c can also enter the cell nucleus and regulate genes²¹⁰. FDA noted in 2026 that the molecule MOTS-c acts on directly is still unknown³.

MOTS-c was first described in 2015 in Cell Metabolism by Lee and colleagues, a team that included Pinchas Cohen¹. CohBar, a company Cohen founded, said in 2021 that he and academic collaborators discovered it in 2012¹². CohBar developed a modified version, CB4211, and tested it in an early-stage human trial completed in 2021¹²¹³. Wells Pharmacy Network nominated MOTS-c for FDA’s compounding list and then withdrew the nomination³.

Benefits: what the research shows

FDA’s review for its July 2026 advisory meeting, dated 11 May 2026, found no published study that gave MOTS-c to people by any route, no studies of how the body absorbs and clears it, and no animal toxicity studies³. All evidence of effects comes from cells and rodents. In mice on a high-fat diet, daily injections reduced weight gain and insulin resistance¹. In a 2021 study, daily injections for 10 days to 2 weeks improved treadmill running in young, middle-aged and old mice². Injections three times a week, started late in life (at about 23.5 months), improved grip strength and walking, but the lifespan gain was only a trend: median lifespan was 6.4% longer, and the survival difference was not statistically significant over the whole study (P=0.23)². Other rodent studies report less weight gain after ovary removal, less bone breakdown and less calcium build-up in blood vessels³. FDA noted that these studies were limited to rodents, had not worked out how the effects change with dose and had not identified what MOTS-c acts on, so their relevance to people is unknown³. The published human studies we found measure only the body’s own MOTS-c³. Muscle and blood levels rose with a single hard cycling session in 10 young men, and blood levels returned to baseline within 4 hours²; in a randomized exercise study of 30 people, the rise after endurance exercise was only a trend¹⁶. Blood levels were lower in older men, while muscle levels were higher¹⁷. A 2024 meta-analysis of 7 observational studies (602 people) found lower blood MOTS-c in type 2 diabetes, and higher levels in obesity once people who were overweight but not obese were left out⁴. In a meta-analysis of three cohorts (27,527 people), men, but not women, carrying an Asian-specific variant that changes one amino acid of MOTS-c had more type 2 diabetes¹⁵. These are associations, not treatment effects. The measurements themselves are in question: an anti-doping lab could not confirm, by mass spectrometry, the blood levels a commercial antibody test (ELISA) reported¹¹. The only related human drug data are for CB4211, a modified analog that is a different molecule. In a company-reported 4-week trial in 20 adults with obesity and fatty liver disease, 25 mg injected under the skin daily lowered the liver enzymes ALT by 21% (placebo: up 4%) and AST by 28% (placebo: down 11%), while liver fat fell about equally in both groups¹². The main side effects were mild to moderate injection-site reactions¹². The trial registry shows no posted results¹³. None of this counts as evidence for MOTS-c itself.

Key human studies

Study	Design	People	Dose and route	Result
Zempo et al., Aging 2021¹⁵PubMed · DOI	Genetic association study: meta-analysis of three cohorts (J-MICC, MEC and TMM), with follow-up experiments in mice; no MOTS-c given to people	27,527	None in humans (a natural gene variant was studied)	Men, but not women, carrying the Asian-specific m.1382A>C variant, which changes the 14th amino acid of MOTS-c (K14Q), had a higher prevalence of type 2 diabetes; in one cohort this held only for the least active men. In high-fat-fed male mice, normal MOTS-c reduced weight and improved glucose tolerance, but the K14Q form did not¹⁵.
Zhou et al., Diabetol Metab Syndr 2024⁴PubMed · DOI	Systematic review and meta-analysis of 6 case-control studies and 1 cross-sectional study of blood MOTS-c; no MOTS-c given	602	None (natural MOTS-c measured)	Across diabetes and obesity combined, blood MOTS-c was lower (standardized mean difference, SMD, -0.37). By subgroup it was lower in type 2 diabetes (SMD -0.89) but higher in obesity (SMD 0.51, once people who were overweight but not obese were excluded). It correlated weakly with total and LDL cholesterol (r = 0.29 and 0.30)⁴.
Reynolds et al., Nat Commun 2021²PubMed · DOI	Human part: one high-intensity stationary cycling session in sedentary healthy young men, with blood sampled before, during and after exercise, muscle before and after, and both again after 4 hours of rest; the paper’s treatment experiments were in mice	10	None in humans (natural MOTS-c measured)	Muscle MOTS-c rose 11.9-fold after exercise and was still raised after 4 hours of rest. Blood levels rose 1.6-fold during and 1.5-fold after exercise, then returned to baseline within 4 hours².
D’Souza et al., Aging 2020¹⁷PubMed · DOI	Cross-sectional study of healthy men aged 18-30, 45-55 and 70-81, with blood samples and thigh-muscle biopsies; no MOTS-c given	104	None (natural MOTS-c measured)	Compared with young men, blood MOTS-c was 11% lower in middle-aged men and 21% lower in older men, while muscle MOTS-c was about 1.5-fold higher in both of those age groups¹⁷.
von Walden et al., J Appl Physiol 2021¹⁶PubMed · DOI	Randomized exercise study: endurance exercise, resistance exercise or no exercise (10 people each); MOTS-c measured, not given	30	None (natural MOTS-c measured)	Endurance exercise raised blood levels of humanin, a related mitochondrial peptide, but blood MOTS-c showed only a trend to rise. Blood levels of these peptides were not linked to fitness¹⁶.

Doses studied

Doses below are what studies used or what a label says. They are not advice, and gray-market products may not contain what their label says.

In human studies

None found. FDA found no published study that gave MOTS-c to people by any route, including injection under the skin, so there is no human dose to report³. Doses used for CB4211, a different, modified molecule, do not apply to MOTS-c¹².

In animal studies

As reported, by injection into the abdominal cavity (IP). Mice: 0.5 mg/kg a day for 8 weeks in mice on a high-fat diet, which gained less weight¹³; 5 mg/kg a day for 7 days in 12-month-old mice, which restored muscle insulin sensitivity³; 5 or 15 mg/kg a day for 10 days to 2 weeks in young mice (on the treadmill, only the higher dose clearly helped), and 15 mg/kg a day for 2 weeks in middle-aged and old mice, before physical performance tests²; 15 mg/kg three times a week from about 23.5 months of age in the late-life study²; and 5 mg/kg a day for 12 weeks in mice whose ovaries were removed³. Rats: 5 mg/kg a day in a model of blood-vessel calcification³. FDA noted that the animal studies have not worked out how the effects change with dose³.

What users report Anecdotal · not validated · not a recommendation

A dosing-calculator site works through amounts from 200 to 1,000 µg (micrograms) per dose, which it calls a calculation model, not a validated human dosing protocol. It says public descriptions range from daily to one, two or three times a week, and that no controlled human trial has set a MOTS-c dose²⁶.

Routes: Subcutaneous injection (the form proposed in the compounding nomination, 5 mg and 10 mg, and the route dosing charts describe; no human data found)
Intraperitoneal injection into the abdominal cavity (animal studies only)
Intravenous drip (FDA found one clinic’s IV ‘cocktail’ listing MOTS-c; no human data found)

Every dose studied for MOTS-c, with sources →

Legal status

United States: MOTS-c is not approved by FDA for any use, and it is not a component of any FDA-approved drug³. In a review dated 11 May 2026, FDA found no published study of MOTS-c products in humans and said the potential safety risks of using it in people are unknown³.
US pharmacies: Under section 503A, pharmacies may compound only with bulk ingredients that have a USP or NF monograph, are part of an FDA-approved drug or are on FDA’s 503A bulks list. Under an interim policy, FDA also does not intend to act against compounding with substances in its ‘Category 1’¹⁸. MOTS-c fits none of these routes. It has no monograph, is in no approved drug and is not on the list³, and it is in no category on FDA’s 503A lists updated 14 May 2026 or its 503B lists for outsourcing facilities updated 21 March 2025⁵¹⁹. It was in Category 2 (substances that may pose significant safety risks) until the nominator withdrew its nomination; FDA now lists it as ‘nominated but withdrawn’ (page current 22 April 2026)²⁰. FDA reviewed MOTS-c and MOTS-c acetate on its own initiative and concluded that the evidence weighs against adding them to the 503A bulks list³. On 23 July 2026 the Pharmacy Compounding Advisory Committee voted 7-5-2 (7 for, 5 against, 2 abstaining) to recommend both forms, against the advice of FDA’s review team, according to the FDA Law Blog³⁶. The vote is advisory; according to the same blog, FDA said it would announce any final decision through notice-and-comment rulemaking⁶. As of 8 October 2026, FDA’s meeting page listed no minutes or transcript²¹. Outsourcing facilities did not report making any MOTS-c products from January 2017 to December 2025³.
Other countries: Canada: Health Canada seized unauthorized injectable peptides including MOTS-c from a Calgary wellness center (April 2025 advisory) and listed MOTS-C among seized products in its 9 April 2026 warning against injecting peptides bought online²²²³. UK: The Guardian reported on 4 April 2026 that the MHRA, the UK medicines regulator, would investigate peptide clinics over health claims, and MOTS-C was among the products named²⁴; UK legal status was not verified. EU: FDA found no MOTS-c product authorized by the European Medicines Agency and no monograph in the European or Japanese pharmacopoeias³. Australia: MOTS-c is not named in the Poisons Standard in force from 1 October 2026²⁵; how Australian law otherwise treats it was not verified.
Sport: Prohibited at all times, in and out of competition. The 2026 list names ‘mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)’ as an example of an AMPK activator in class S4.4.1, whose substances are non-Specified, and the 2027 list published 21 September 2026 keeps the same entry⁷⁸. A mass-spectrometry test for MOTS-c in blood plasma, validated to WADA laboratory standards, was published in 2019¹¹.

MOTS-c in the legal tracker →

Quality and the gray market

What testing finds

Finnrick, an independent testing service, reported 77 tests of gray-market MOTS-c from 20 vendors between 20 February 2026 and 24 September 2026: 22 passed, 52 failed and 3 were incomplete under its default standard (purity of at least 99.5% and content within 35% of the label)⁹. FDA found no public data on impurities, clumping (aggregation) or bacterial endotoxin for MOTS-c ingredients³. The nomination included no certificate of analysis for the free form, and the one for the acetate salt gave no results for impurities, aggregates, microbes or endotoxin³. FDA also noted that ‘MOTS-c’ is a common name, not an official drug name, and that for similar products it has seen different salts and derivatives sold under one name³.

How it is sold

MOTS-c is sold online by peptide vendors, often spelled MOTS-C. It was among the top four items on two vendors’ popularity-sorted shop pages (accessed 30 September 2026)²⁷²⁸. By our count from the chart data on Finnrick’s June 2026 insights page, MOTS-c drew 154 of 21,253 test requests from May 2025 to May 2026 (about 0.7%)²⁹. Clinics offer it too. In pages it viewed in March 2024, FDA found a holistic clinic that said it obtains compounded MOTS-c from pharmacies and a wellness clinic promoting a ‘Cocktail IV Therapy’ containing MOTS-c³. Websites market it for weight loss, blood sugar control, physical performance, muscle health and slower cellular aging³. In Canada, Health Canada has seized MOTS-C products from a wellness center and listed it among examples of seized products in an April 2026 warning²²²³.

Side effects and risks

Unknown human safety: FDA found no human safety data and no animal toxicity studies (single-dose, repeated-dose, genetic, reproductive or cancer) for MOTS-c, so its risks in people are unknown³.
Immune reactions: FDA says injected MOTS-c may pose a significant risk of immunogenicity, an unwanted immune response, because of peptide-related impurities and clumping³²⁰.
Product quality: 52 of 77 gray-market samples tested by Finnrick in 2026 failed its purity-and-dose standard, so a vial may not contain what its label says⁹.
Unknown behavior in the body: FDA found no study of how injected MOTS-c is absorbed or cleared, and in a test-tube study it broke down quickly in human blood, so it is unknown whether injections reach active levels³.
Missing reports: FDA’s adverse event database had no MOTS-c reports through 9 March 2025, but pharmacies compounding under section 503A generally do not report adverse events to FDA, so no reports does not mean no harm³.
Anti-doping: MOTS-c is prohibited at all times as a non-Specified substance in WADA class S4.4.1, and a lab test for it has been published⁷¹¹.
Legal: US pharmacies have no lawful 503A route to compound it, and Health Canada has seized unauthorized MOTS-C products⁵²³.

Questions people ask

What is MOTS-c?

MOTS-c is a 16-amino-acid peptide whose code sits in mitochondrial DNA. In cell and mouse studies it acts mainly on muscle and improves how the body handles sugar, partly by switching on the energy sensor AMPK¹.

Has MOTS-c been tested in humans?

Not in any published study that FDA found. Its 2026 review found no published study that gave MOTS-c to people; the published human studies we found only measure the body’s own levels²³. A modified analog, CB4211, was tested in a small trial that ended in 2021, but it is a different molecule¹²¹³.

What are the side effects of MOTS-c?

No one knows: FDA found no safety data in people and no animal toxicity studies³. FDA says injections may trigger an unwanted immune response because of impurities and clumping³²⁰. FDA’s adverse event database had no MOTS-c reports through 9 March 2025, but compounding pharmacies generally do not report adverse events to FDA, so that does not show it is safe³.

Is MOTS-c FDA approved or legal to compound?

It is not FDA-approved, and as of 8 October 2026 it was in no 503A category, so pharmacies have no lawful route to compound it³⁵. An FDA advisory panel voted 7-5-2 on 23 July 2026 to recommend adding it to the compounding list, according to the FDA Law Blog, but that vote is advisory⁶.

Does MOTS-c help with weight loss or longevity?

That has only been shown in rodents. Mice given MOTS-c gained less weight on a high-fat diet, and old mice ran and gripped better, but their longer lifespan was only a statistical trend¹².

What MOTS-c dose has been studied?

FDA found no published study that gave MOTS-c to people, so there is no human dose to report³. Mouse studies used 0.5 to 15 mg/kg injected into the abdominal cavity¹². These animal doses are not human doses, and online dosing charts are not based on trials¹²²⁶.

Is MOTS-c banned in sports?

Yes. WADA prohibits it at all times, in and out of competition, as an AMPK activator in class S4.4.1 on both its 2026 and 2027 lists⁷⁸.

What is still unknown

Whether MOTS-c given by injection is safe or does anything in people; we found no published human results.
Whether a Phase 2a MOTS-c trial listed on ClinicalTrials.gov (NCT07505745, first posted 1 April 2026 and marked as recruiting at one site in China) is under way as described; its sponsor could not be verified and no results are posted.
How long injected MOTS-c lasts in the body; FDA found no in-vivo pharmacokinetic studies, only a test-tube study showing fast breakdown in human blood.
Whether the lifespan trend in old mice (Reynolds 2021) holds up; the authors said larger groups of mice are needed.
How accurately commercial antibody tests (ELISA) measure natural MOTS-c; an anti-doping lab could not confirm ELISA values by mass spectrometry.
What FDA will decide after the 23 July 2026 advisory vote; no minutes had been posted and the 503A category lists had not changed as of 8 October 2026.
What happened to CB4211 after its trial ended in 2021; its later development status was not verified.
The legal status of MOTS-c products in the UK and EU, and how Australian law treats it; not verified.

Sources

1The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance Cell Metabolism, 3 Mar 2015. pubmed.ncbi.nlm.nih.gov
2MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis Nature Communications, 20 Jan 2021. pubmed.ncbi.nlm.nih.gov
3July 23-24, 2026, Meeting of the Pharmacy Compounding Advisory Committee – FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate) U.S. Food and Drug Administration, 11 May 2026. fda.gov
4The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis Diabetology & Metabolic Syndrome, 19 Aug 2024. pubmed.ncbi.nlm.nih.gov
5Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories list) U.S. Food and Drug Administration, 14 May 2026. fda.gov
6PEPTIDE-L WAVE! PCAC Approves Four Bulk Drug Substances for the 503A List FDA Law Blog (Hyman, Phelps & McNamara), 24 Jul 2026. thefdalawblog.com
7World Anti-Doping Code International Standard: Prohibited List 2026 World Anti-Doping Agency, 24 Sep 2025. wada-ama.org
8World Anti-Doping Code International Standard: Prohibited List 2027 World Anti-Doping Agency, 21 Sep 2026. wada-ama.org
9MOTS-c: safety testing results and vendor ratings Finnrick, 24 Sep 2026. finnrick.com
10MOTSC_HUMAN (A0A0C5B5G6): Mitochondrial-derived peptide MOTS-c UniProt, 2 Sep 2026. uniprot.org
11Development of a mass spectrometry based detection method for the mitochondrion-derived peptide MOTS-c in plasma samples for doping control purposes Rapid Communications in Mass Spectrometry, 28 Feb 2019. pubmed.ncbi.nlm.nih.gov
12CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and Obesity (Form 8-K, Exhibit 99.2) CohBar, Inc. (SEC EDGAR filing), 10 Aug 2021. sec.gov
13A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease (NCT03998514) ClinicalTrials.gov, 11 May 2021. clinicaltrials.gov
14Mots-c, CID 146675088 PubChem, U.S. National Library of Medicine, accessed 1 Oct 2026. pubchem.ncbi.nlm.nih.gov
15A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c Aging (Albany NY), 19 Jan 2021. pubmed.ncbi.nlm.nih.gov
16Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans Journal of Applied Physiology, 1 Sep 2021. pubmed.ncbi.nlm.nih.gov
17Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition Aging (Albany NY), 17 Mar 2020. pubmed.ncbi.nlm.nih.gov
18Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act U.S. Food and Drug Administration, 14 May 2026. fda.gov
19Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories list) U.S. Food and Drug Administration, 21 Mar 2025. fda.gov
20Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks U.S. Food and Drug Administration, 22 Apr 2026. fda.gov
21July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee U.S. Food and Drug Administration, 6 Aug 2026. fda.gov
22Unauthorized injectable peptide drugs seized from Optimum Wellness Centre in Calgary, Alberta may pose serious health risks (RA-77218) Health Canada, 1 Apr 2025. recalls-rappels.canada.ca
23Think twice before injecting peptides bought online: unauthorized products can seriously harm you (RA-81874) Health Canada, 9 Apr 2026. recalls-rappels.canada.ca
24Medicines watchdog to investigate UK peptide clinics over health claims The Guardian, 4 Apr 2026. theguardian.com
25Therapeutic Goods (Poisons Standard—October 2026) Instrument 2026 (F2026L01327) Federal Register of Legislation, Australian Government, 28 Sep 2026. legislation.gov.au
26MOTS-C (10 mg Vial) Dosage Protocol PeptideDosages, 24 Sep 2026. peptidedosages.com
27Ascension Peptides shop page sorted by popularity Ascension Peptides (vendor), accessed 30 Sep 2026. ascensionpeptides.com (seller page, deliberately not linked)
28Prime Peptides shop page sorted by popularity Prime Peptides (vendor), accessed 30 Sep 2026. primepeptides.co (seller page, deliberately not linked)
29We’d Rather Buy the Future Than Wait For It Finnrick, 10 Jun 2026. finnrick.com

Not medical advice. This page reports what studies and regulators say; it does not recommend using any product. How we grade evidence · Report an error.