MOTS-c side effects: what has actually been recorded

What are the side effects of MOTS-c?

No published human trial recording side effects of MOTS-c itself was found in the sources searched for this page. The nearest record is the Phase 1a/1b trial of CB4211, a MOTS-c analogue, which enrolled 88 people according to the registry (ClinicalTrials.gov NCT03998514). Its sponsor reported that the drug was well tolerated, that there were no serious adverse events, and that the only adverse events in more than 10% of participants who received CB4211 in the four-week stage (20 obese adults with fatty liver disease) were transient, generally mild-to-moderate reactions at the site where the drug was given; the report is a company press release about an analogue, a different molecule, so none of it transfers to MOTS-c directly (CohBar press release, 10 August 2021).

Two cautions apply. The report came from the sponsor as a press release, and the registry entry lists no results. A PubMed search on 14 October 2026 for the compound code CB4211 returned no paper. The numbers are a company's account and have not been independently checked.

The site reactions had a history. The sponsor's annual report for fiscal year 2022 says the Phase 1a/1b trial of CB4211 was suspended in November 2018 to address reactions at the site where the drug was given, and that the formulation was modified partway through the Phase 1a stage in healthy subjects (CohBar Form 10-K for fiscal year 2022, filed 9 March 2023). The same CohBar Form 10-K says the formulation used in Phase 1b is not believed to be suitable for further development and that efforts to develop an improved formulation had not been successful to date. These are sponsor statements about an analogue, give no participant count for Phase 1a and do not establish MOTS-c safety.

Searches that pair 'benefits and side effects' blend two different questions: what animals did in experiments, and what people experienced. In the sources searched for this page, the second kind of evidence for MOTS-c is almost empty.

What do studies and reviews say about the safety of MOTS-c?

The sources read describe the safety of MOTS-c in people as unestablished. A 2026 narrative review of 106 articles on therapeutic peptides states that for MOTS-c the data are almost exclusively preclinical, with no major signs of toxicity, but without robust evidence in humans, and it tested nothing itself (Renke and Chinellato, International Journal of Molecular Sciences, 2026). A 2026 narrative review covering twelve peptides, MOTS-c among them, states that rigorous human safety data are scarce for many unapproved peptides, and it likewise reports on other studies (Mendias and Awan, Sports Medicine, 2026). The FDA says it lacks important information regarding any safety issues raised by MOTS-c, including whether it would cause harm in humans (FDA compounding page, current as of 22 April 2026).

Safe is a word that needs a population, a duration and a route behind it. For MOTS-c, no published human trial found in the sources searched supplies any of the three. The sections below show what has and has not been tested.

Evidence limits

What has never been tested for MOTS-c?

The registry entry for that trial lists treatment-emergent adverse events through 16 weeks as a primary outcome and anti-drug antibodies as a secondary one. It excludes pregnancy, breastfeeding, active cancer treatment and significant liver, kidney or heart disease (ClinicalTrials.gov NCT07505745, record updated 1 April 2026).

A mouse study adds a different kind of limit. In cell-free tests and mouse experiments, MOTS-c switched on the enzyme CK2 in muscle but switched it down in fat, and the authors wrote that 'it remains unclear whether MOTS-c exerts adverse effects in these tissues', a statement about mice that leaves the human question open (Kumagai et al., iScience, 2024). The site catalogue lists MOTS-c reference material as a laboratory reference, not a medicine and not for human or animal use.

What did the human trial of a MOTS-c analogue record?

The CB4211 trial was randomised, double-blind and placebo-controlled, with three parts: two parts in healthy adults and a four-week part in obese adults with fatty liver disease (ClinicalTrials.gov NCT03998514). The sponsor described 65 healthy adults in the first stage and 20 obese adults in the second, which differs from the 88 enrolled according to the registry, so the two records do not fully agree (CohBar press release, 10 August 2021). The registry lists adverse events, laboratory results, vital signs, ECG, physical examination and assessments of the site where the drug was given as primary outcomes (ClinicalTrials.gov NCT03998514).

Eligibility shaped what could be seen. Participants were adults aged 18 to 60, and women had to be unable to become pregnant. People with kidney impairment, significant liver or heart-rhythm abnormalities, active infection, hepatitis or HIV were excluded, and healthy participants had to start with normal liver enzymes (ClinicalTrials.gov NCT03998514). A trial like that can reveal common, early problems in a selected group. It cannot reveal rare problems or problems in the people it left out.

In the 20 adults with fatty liver disease in the second stage (11 on CB4211 and 9 on placebo), the sponsor also reported lower liver-enzyme levels than placebo, an exploratory result from a company press release about a different molecule that says nothing further about side effects (CohBar press release, 10 August 2021).

Does MOTS-c cause cancer or change tumour growth?

No study testing whether MOTS-c exposure changes cancer risk in people was found in the sources searched. In ovarian cancer cells and a mouse tumour model, added MOTS-c slowed growth without reported systemic toxicity, a laboratory and mouse result that does not establish an effect or safety in people (Yin et al., Advanced Science, 2024). Yin et al. found lower serum MOTS-c in 40 ovarian cancer patients than in 40 healthy women, and lower tumour-tissue MOTS-c than in adjacent normal tissue in analyses of 10 patients and 247 paired tissue samples; these observational comparisons did not test supplied MOTS-c (Advanced Science, 2024). In liver cancer cells and nude mice, MOTS-c restored the cells' sensitivity to TRAIL-triggered cell death under low oxygen and reduced hypoxia-induced tumour growth, a cell and mouse result that does not establish cancer effects or safety in people (Shen et al., Experimental Cell Research, 2025).

Not every finding runs in the same direction. In cultured senescent cells, meaning ageing cells that have stopped dividing, MOTS-c and humanin each increased release of inflammatory signals, including IL-6, IL-8 and TNF-alpha, a culture result summarised in a 2018 review whose meaning in a living person is not known (Mendelsohn and Larrick, Rejuvenation Research, 2018). In a mouse bone-cancer model, chronic MOTS-c treatment had little effect on liver, renal, lipid or cardiac function, a mouse result that does not establish human safety (Yang et al., Acta Biochimica et Biophysica Sinica, 2024).

Human cancer data are about the body's own MOTS-c, not about supplied MOTS-c. In a secondary analysis of a 16-week exercise trial in 49 breast cancer survivors (24 non-Hispanic White and 25 Hispanic), the body's own MOTS-c rose in non-Hispanic White participants but not in Hispanic participants; this small exercise trial did not test supplied MOTS-c or cancer risk (Dieli-Conwright et al., Scientific Reports, 2021). The CB4211 registry record lists adverse-event time frames of up to 12 weeks, and the MOTS-c trial record lists adverse events through 16 weeks; neither record reports a cancer outcome, which is why the question stays open.

What does the FDA say about MOTS-c safety?

The FDA's compounding page, current as of 22 April 2026, lists MOTS-c among bulk drug substances whose nominations were withdrawn. It states that the agency has not identified any human exposure data on drug products containing MOTS-c. It adds that compounded drugs containing MOTS-c may pose significant risk for immunogenicity, with a route qualifier stated on that page, and may have 'complexities with regard to peptide-related impurities and API characterization'. The page groups MOTS-c with other peptides whose nominations were withdrawn, including BPC-157 and CJC-1295.

Immunogenicity means the immune system treating a peptide as foreign and making antibodies against it. API characterisation means pinning down exactly what the active ingredient is and what else is in the product. Notice what the FDA page does not say: it does not report any harm. It reports missing information, and missing information is neither a clean bill of health nor a warning of injury.

The registry record for the MOTS-c trial lists anti-drug antibodies as a secondary outcome (ClinicalTrials.gov NCT07505745). The Australian law guide explains how Australian rules treat peptide products, and the MOTS-c in Perth page covers the sport listing.

Has the half-life of MOTS-c been measured in people?

No human half-life for MOTS-c was found in the sources searched as of 14 October 2026. A PubMed search for MOTS-c with pharmacokinetic terms returned three records: a review of MOTS-c in sepsis-related heart injury, an isolated rat-heart experiment and a colitis study in mice. The abstracts of those three records did not report a half-life in people, meaning the time it takes for the amount in the blood to fall by half. The CB4211 registry record lists half-life and clearance of the analogue as secondary outcomes in a trial of 88 participants, but posts no results (ClinicalTrials.gov NCT03998514).

What has been measured in people is the body's own peptide. In 10 sedentary healthy young men cycling on a stationary bicycle, circulating MOTS-c rose to about 1.6 times its starting level during exercise and about 1.5 times afterwards, then returned to baseline after four hours of rest, while muscle MOTS-c rose about 11.9-fold; this describes the behaviour of a natural signal in one small group, not the clearance rate of a supplied peptide (Reynolds et al., Nature Communications, 2021).