MOTS-c

16 amino acids

Native MOTS-c is linked to a short sequence within mitochondrial DNA. Its production and secretion are still being worked out. CB4211 is a modified analogue with a separate human trial.^179,180,181

What was studied	What it can show
Natural MOTS-c in people	Associations with health and changes during exercise. These studies do not establish the effects of injected MOTS-c.182
Native MOTS-c in mice and cells	Effects on glucose metabolism, stress responses and physical function under experimental conditions. Human benefit and safety remain separate questions.183,184,182
CB4211 in people	A different molecule studied in a phase 1 trial. Its results cannot be assigned to native MOTS-c.181

Exercise and aging

The best-known exercise paper studied people and mice in different ways. Only the mice received MOTS-c.

10 men

In ten sedentary healthy young men, muscle MOTS-c rose 11.9-fold after a cycling session. Circulating levels rose 1.6-fold during exercise and 1.5-fold afterward, then returned to baseline after four hours. Nobody received MOTS-c.¹⁸²

The mouse experiments

Separate experiments found better running performance in young, middle-aged and old mice given MOTS-c. The older mice also showed improvements in physical-function tests. These results support further research, but they cannot predict how much energy, endurance or recovery a person would gain.¹⁸²

Lifespan result

The same paper reported a trend toward longer lifespan in treated old mice. The overall survival comparison was not statistically significant (P = 0.23). The physical-function findings should not be rewritten as proven lifespan extension in mice or people.¹⁸²

Assay comparison

A 2019 laboratory study compared two methods in samples from 20 healthy people. The MOTS-c readings from an antibody-based assay could not be confirmed with liquid chromatography and mass spectrometry. This raises a measurement question; it does not show that every published assay result is wrong.¹⁸⁸

A retracted bone-healing paper

A 2019 fracture-healing paper was retracted after image-organization inaccuracies were identified. It is excluded from the evidence used here. Other bone studies must stand on their own results.¹⁸⁹

Human analogue trial

CB4211 is a modified analogue. Its small human trial cannot tell us whether native MOTS-c works or is safe.

88 enrolled

The study enrolled 65 healthy adults and 23 people with fatty liver disease. In the fatty-liver cohort, 20 completed the final four-week assessments: 11 received CB4211 and nine received placebo. Two participants stopped because of COVID-19 and one withdrew consent.^181,190 The phase 1b study used 25 mg of the analogue subcutaneously once daily for four weeks. This describes the study, not a native-MOTS-c dosing recommendation.^190,191

Early signals, limited conclusions

The sponsor reported a 21% decrease in ALT compared with a 4% increase with placebo, and a 6% glucose decrease compared with no change. These were exploratory biomarkers. Liver fat fell by similar amounts in both groups, which received a standardized inpatient diet. Weight loss was a trend.^190,191

One result conflicts across reports

The investor presentation reports a 28% AST reduction with CB4211. The later conference abstract reports 18%; both give 11% for placebo. The discrepancy remains unresolved. A conference abstract and investor slides are not a full clinical trial report.^190,191

Tolerability and formulation problems

The sponsor reported no serious adverse events and injection-site reactions in 79% of CB4211 recipients versus 33% with placebo in its combined phase 1 presentation. The safety slide does not specify that calculation's denominator. A later filing said the phase 1b formulation was unsuitable for further development and improvement attempts had been unsuccessful.^190,192

Safety and status

Injected-product safety requires evidence beyond natural occurrence, promising mouse results and a clean-looking certificate.

Human half-life

FDA's May 2026 review found no clinical pharmacokinetic data for native MOTS-c. An experiment measured peptide breakdown in collected human blood.¹⁸⁷

Adverse-event counts have limits

FDA reported finding no FAERS reports in searches ending March 9, 2025. That is a historical result. The current event-data query could not be completed, so the current count is unknown. Neither finding establishes safety or an adverse-effect rate.¹⁸⁷

Product-characterization gaps

FDA identified missing information about impurities, aggregation, bioburden and endotoxins. These were gaps in characterization, not a measured contamination rate. Canadian alerts also named unauthorized products labeled MOTS-c without establishing their chemical contents.^{187,132,194,195}

US compounding review

FDA staff recommended against adding the evaluated MOTS-c forms to the 503A bulk-substances list. The current risk page lists MOTS-c among substances whose nominations were withdrawn. The committee's exact vote and any final action were not verified in the available records; neither a nomination nor an advisory discussion is drug approval.^187,196,197

New Zealand group classification

New Zealand classifies mitochondria-derived peptides and their analogues as prescription medicines. MOTS-c is included in the underlying group proposal. A search showing no individual MOTS-c entry leaves the group restriction in place; prescription classification alone confers no product approval.^198,199

Prohibited in sport

WADA explicitly names MOTS-c under S4.4.1, the AMPK-activator category, prohibited at all times. It appears in both the 2026 list and the published 2027 list. A doping rule does not establish medical benefit or approval.^200,201

Common questions

Questions cover results, combinations, timing and safety.

01 What changes when MOTS-c is combined with SS-31, NAD+, GLP-1 drugs or other peptides?

No controlled clinical combination outcome was identified in the sources behind this chapter. Separate studies of other compounds cannot predict the benefit, interaction risk or exposure of a stack, especially when product identity is uncertain. The evidence does not support mixing, sequencing or timing instructions.^187,181

02 What doses, timing, schedules and cycle lengths have actually been studied?

No administered-native human dose or cycle was verified. The foundational studies used experiment-specific intraperitoneal exposure in mice; separate sponsor sources report 25 mg CB4211 subcutaneously once daily for four weeks, while the registry itself omits actual dose values. That historical analogue exposure is not a native-MOTS-c regimen or a recommendation.^{183,182,181,190,191}

03 What did the CB4211 study actually report?

CB4211, not native MOTS-c, enrolled 88 people across phase 1a/1b; 20 participants, 11 active and 9 placebo, reached the final four-week pharmacodynamic analysis. Sponsor and conference reports gave ALT changes of -21% versus +4% and glucose changes of -6% versus 0%, while liver fat fell by similar amounts; AST differed between sources, -28% versus -18% for active, with -11% for placebo in both. The safety slide reported injection-site reactions of 79% versus 33% without an explicit denominator, the registry posts no results, and a later filing said the phase 1b formulation was unsuitable for further development.^{181,190,191,192}

04 What is known about fatigue, hunger, injection reactions, allergy and other adverse effects?

A native-MOTS-c adverse-effect rate in people is unknown because no credible administered-human study was verified. FDA identified potential immunogenicity and major characterization gaps, while CB4211 injection-site reactions belong to that analogue and formulation. Forum reports of fatigue, hunger or allergy explain the question but cannot establish frequency or causality.^{187,196,190,192}

05 Does MOTS-c cause weight or fat loss, or improve glucose control, diabetes or insulin resistance?

Mouse experiments reported changes in glucose handling and insulin sensitivity and, when MOTS-c was given during high-fat feeding, less weight gain. That prevention design is not evidence of weight loss or diabetes treatment in people, and human endogenous associations do not show a treatment effect. The small CB4211 analogue cohort reported exploratory biomarkers, not native-MOTS-c efficacy.^{183,181,190,191}

06 Were oral or injected forms studied, and do studies support reconstitution or storage claims?

The foundational native-MOTS-c studies used intraperitoneal injections in mice, and the separate CB4211 trial used subcutaneous injections in people. No credible administered-native human study or product-specific preparation and stability study was verified. These records do not support choosing a route or giving reconstitution, storage or vial-handling instructions.^{183,182,181,187}

07 Is MOTS-c an exercise replacement or proven recovery aid?

No verified human treatment trial behind this chapter tested that claim. In ten sedentary healthy young men, cycling raised endogenous muscle MOTS-c 11.9-fold and plasma levels 1.6-fold during and 1.5-fold after exercise, with plasma back to baseline after four hours; the men did not receive MOTS-c. Separate treated-mouse performance findings cannot establish human energy, endurance or recovery benefit.¹⁸²

08 What is known about half-life, onset, duration and what happens after stopping?

No clinical native-human half-life, onset or washout was verified. FDA cited an experiment in collected human blood, but that measured in-vitro degradation rather than clearance after injection. Mouse timing and the separate CB4211 program cannot supply a native-human duration or dosing interval.^187,188,181

09 Is MOTS-c approved or legal, what is its compounding status, and is it prohibited in sport?

The checked US records contained no FDA-approved MOTS-c product, and FDA staff recommended against 503A inclusion in its May 11, 2026 assessment for the July 23 meeting. New Zealand classifies mitochondria-derived peptides and their analogues as Prescription, which is not medicine approval; other jurisdictions require their own current check. The effective 2026 WADA list and the published 2027 list both name MOTS-c under S4.4.1 as prohibited at all times, and China's official 2026 Doping Catalogue also names it.^{202,187,197,198,199,200,201,203}

10 Can a vial be authenticated, and what do vendor, purity, storage and sourcing claims prove?

A label or certificate alone does not verify sequence, salt, amount, purity or sterility. FDA found missing impurity, aggregation, bioburden and endotoxin characterization in the nominations, which is missing evidence rather than proof of a market-wide contamination rate. Canadian alerts name unauthorized products labeled MOTS-c without establishing their chemical contents.^185,187,132

11 Can CB4211 results be applied to native MOTS-c?

No. Native MOTS-c has the 16-residue sequence MRWQEMGYIFYPRKLR, while CB4211 is an engineered analogue with a separate formulation and clinical record. CB4211 pharmacokinetics, biomarker changes and injection reactions cannot be assigned to native MOTS-c.^{179,185,181,187}

12 What do cancer and tumor studies show, and do they establish human benefit or risk?

Cell, animal and endogenous-association findings cannot determine a human benefit or risk rate. The clinical sources behind this chapter contained no native-MOTS-c treatment outcome for cancer, and in its May 2026 review FDA found no nonclinical carcinogenicity or genotoxicity studies for the nominated native forms. Cell, animal or endogenous-association findings should not be rewritten as cancer treatment or proof of safety.¹⁸⁷

13 Does MOTS-c slow aging or extend lifespan in people?

No verified study behind this chapter showed lifespan extension in people. Late-life-treated old mice improved on physical-function measures, but the overall survival comparison was not statistically significant, P = 0.23. A restricted analysis through 31.8 months should not be presented as proven lifespan extension.¹⁸²

14 What is known for pregnancy, women, adolescents and other special populations?

No administered-native safety study in pregnancy, adolescents or other special populations was verified. FDA found no nonclinical developmental or reproductive toxicity studies for the nominated native forms. Observational measurements in children, women or patient cohorts do not establish safety after administration.^187,204,205

15 What human evidence exists besides the CB4211 analogue trial?

The human sources behind this chapter measured endogenous MOTS-c during exercise, in disease cohorts, in genotype associations or as an outcome of another intervention; they did not administer native MOTS-c. The Hudson listing has no posted results and is excluded from clinical evidence under the sponsor screen because actual conduct was not verified. Regional portal gaps prevent a universal claim that no person anywhere has received it.^{182,188,205,206,204,207}