MOTS-c Dosage: What Studies Used and What Is Still Unknown

Is there a tested MOTS-c dosage for people?

No tested MOTS-c dosage for people exists. MOTS-c is a small peptide, a short chain of amino acids. It is made from the DNA inside your mitochondria, the cell's power plants. The US Food and Drug Administration (FDA) reviewed it in 2026. It found no clinical studies or human exposure data for MOTS-c by any route.

Every dose with a source comes from animals, or from a trial of CB4211. CB4211 is an analogue of MOTS-c, meaning a modified copy of the molecule. So none of the figures below is a dose for people.

The studies gave MOTS-c by injection. Mouse studies injected it into the belly. The CB4211 trial gave the analogue under the skin. A lab study cited by the FDA found MOTS-c breaks down quickly in human blood. The FDA says it is not yet known whether giving MOTS-c to people could reach active levels over time.

MOTS-c dosage chart: doses used in studies

This MOTS-c dosage chart lists the doses that published studies used. Each row names its source. Mouse and rat doses are given per kg of body weight.

The FDA notes that the animal studies did not test dose-response, meaning how an effect changes as the dose changes. No row is tied to a safe or useful dose in people.

MOTS-c dosage per day: what did studies give?

The daily doses in the research are animal doses, plus one analogue trial. In Lee 2015, mice on a high-fat diet got 0.5 mg per kg a day. In Reynolds 2021, old mice got 15 mg per kg a day for 2 weeks.

One daily figure comes from people. In the Phase 1b part of the CB4211 trial, the company says 20 adults with obesity and nonalcoholic fatty liver disease took part. That is a build-up of fat in the liver not caused by alcohol. They got 25 mg of CB4211, or a placebo, once a day under the skin for four weeks. A placebo is a dummy injection. That was the analogue, not native MOTS-c. So it is not a daily dose for MOTS-c itself.

MOTS-c dosage per week: what is known?

No study has set a weekly MOTS-c dosage for people. One mouse study used a weekly schedule. In Reynolds 2021, old mice got 15 mg per kg three times a week, from about 23.5 months of age. Near the end of life, they had better grip strength, stride length and walking ability.

The quick breakdown in human blood is a lab finding. No study has tested how often people would need a dose.

Is there a MOTS-c dosage protocol in the research?

No published MOTS-c dosage protocol for people exists. We found no study that starts low and steps up a MOTS-c dose in humans.

The FDA review found no clinical studies of MOTS-c. Zheng 2023, a review, says no effective way of using MOTS-c in the clinic has been developed. The CB4211 trial is registered as NCT03998514. It tested single and multiple doses of the analogue, and it lists no posted results.

Does timing change the MOTS-c dosage?

No study has tested the timing of a MOTS-c dose in people. We found no primary source on morning doses or on dosing before exercise.

What studies do show is a link with exercise. In Reynolds 2021, 10 sedentary young men did a hard cycling session. MOTS-c in thigh muscle rose about 11.9-fold after exercise. In blood, it rose 1.6-fold during exercise and 1.5-fold after it. Blood levels were back to baseline after 4 hours of rest. In Lee 2015, MOTS-c switched on AMPK in cells. AMPK is an enzyme that acts as the cell's energy sensor. Kim 2019 calls MOTS-c an exercise mimetic, meaning something that copies part of what exercise does.

Is there a MOTS-c dosage for weight loss?

No. There is no published MOTS-c dosage for weight loss in people.

Here is what the evidence does cover. In Lee 2015, mice on a high-fat diet got 0.5 mg per kg of MOTS-c a day. They gained less weight than mice on the same diet without it. Food intake was the same in both groups. The CB4211 trial ran in adults with obesity and fatty liver disease. It measured liver enzymes and blood glucose. The company reported a trend toward lower body weight after four weeks.

So the direction of travel is interesting. A dose for fat loss in people has not been tested.

Is there a set cycle length for MOTS-c dosage?

There's no published human evidence defining an optimal MOTS-c cycle length. We found no primary source for on and off cycles, breaks between cycles, or loss of effect over time.

The longest human data come from the analogue trial. In that trial, the fatty liver part gave CB4211 for 28 days. The registry tracked side effects for up to 12 weeks. We found no human safety data for MOTS-c or CB4211 over a longer period.

MOTS-c peptide human dosage: what the evidence shows

It's thin. The one human trial we found used CB4211, a MOTS-c analogue, not native MOTS-c. The registry lists it as completed, with 88 people enrolled.

CohBar, the company behind CB4211, released topline results in 2021. Topline results are the first headline figures, released before a full report. It said Phase 1a, the first safety stage, tested single and repeat doses over one week in 65 healthy adults. Phase 1b was in 20 adults with obesity and fatty liver disease, dosed at 25 mg a day under the skin for four weeks.

The company marked all three as statistically significant against placebo. That means the gap was unlikely to be down to chance alone. It reported no serious adverse events, meaning no serious harms during the trial. We found no peer-reviewed paper on these results. That's an encouraging early signal. It's still an analogue molecule in a small, short trial. It doesn't validate any native MOTS-c dosing protocol.

Preclinical work goes further, into the heart. In a rat model of type 2 diabetes, daily MOTS-c at 15 mg per kg for three weeks raised mitochondrial respiration in heart tissue. Mitochondrial respiration is how the cell's power plants use oxygen to make energy. Fasting glucose fell, and the heart was less enlarged (Pham 2025).

Separate work looked at cell membrane repair. Ischemia and reperfusion means blood flow is cut off and then restored. In Jia 2024, MOTS-c helped move TRIM72, a membrane-repair protein, to damaged membranes. It also blunted membrane damage from ischemia and reperfusion and preserved heart function.

Both are preclinical findings from animal and cell studies, not human trial evidence. Read them as support for the biology, not proof of human benefit.

Is any MOTS-c dosage safe, and is it banned in sport?

MOTS-c side effects in people are unknown. The FDA concluded that the potential safety risks in humans are unknown. It is concerned about immunogenicity, the risk of the immune system reacting to the peptide. It says this risk may be higher with injection under the skin. The FDA found no animal toxicity studies of MOTS-c.

MOTS-c is not approved by the FDA for human use. In its review dated 11 May 2026, the FDA proposed not adding MOTS-c to the 503A bulks list. That is the list of substances pharmacies may use to compound, meaning custom-make, drugs. The FDA says it will not decide until it has weighed its advisory panel's advice.

In sport, the FDA review notes that MOTS-c is listed as prohibited in Global DRO (Global Drug Reference Online). Athletes use this online tool to check whether a substance is banned in sport. That listing draws on the 2024 Prohibited List of the World Anti-Doping Agency (WADA).

For CB4211, the company said the only adverse events in more than 10% of people on it were injection-site reactions. It called them transient, meaning short-lived, and generally mild to moderate. There's no chronic-use human data for native MOTS-c. There's no established safe upper dosing threshold either.

Is there a MOTS-c dosage for stacking with NAD+?

No. We found no published human trial that tested MOTS-c with NAD+. NAD+ is a molecule cells use to make energy. So there is no tested MOTS-c dosage for a stack with it.

One 2025 study touches on both. Kong 2025 found MOTS-c levels fall with age in mouse pancreatic islet cells, the cells that make insulin. MOTS-c treatment reduced cell senescence, meaning cells that stop dividing and stop working well. It did so in islet cells taken from old mice and treated in the lab, and in two diabetes mouse models. Glucose tolerance, how well the body clears sugar from the blood, improved in both diabetes models.

The paper did not show MOTS-c raising NAD+ in islets. It cites earlier cell work in which extra MOTS-c raised NAD+ levels. It also found MOTS-c lowered the gene message for CD38, an enzyme that uses up NAD+, in insulin-making cells. That is a lab link, not confirmed benefit from taking the two together.

How does MOTS-c work, and why does it matter for MOTS-c peptide dosage?

MOTS-c is a peptide of 16 amino acids. Your mitochondrial DNA encodes it, not your nuclear genome. The nuclear genome is the main DNA, kept in the cell's nucleus. Lee 2015 first described it. The name stands for mitochondrial open reading frame of the 12S rRNA-c. An open reading frame is a stretch of DNA that can code for a protein. 12S rRNA is a gene in mitochondrial DNA.

In cell studies, MOTS-c slows the folate cycle, a chain of reactions that helps cells make DNA building blocks. A molecule called AICAR then builds up, and AICAR turns on AMPK. In mice, MOTS-c treatment prevented insulin resistance from age and from a high-fat diet. Insulin resistance is when cells respond poorly to insulin. It also prevented diet-induced obesity (Lee 2015). Lee 2016, a review by the same team, says MOTS-c targets skeletal muscle and boosts glucose metabolism.

Under metabolic stress, MOTS-c moves into the cell nucleus. There it controls genes that carry antioxidant response elements, switches that help cells cope with stress (Wan 2023). In mice on a high-fat diet, MOTS-c raised levels of GLUT4, a transporter that moves glucose into muscle cells.

The first 11 building blocks of MOTS-c are highly conserved among 14 species, including humans and mice. Highly conserved means nearly unchanged from species to species. In people, exercise raises MOTS-c in muscle and blood. Levels in blood fall with age. In one group of men, blood MOTS-c was lower in those with higher fasting insulin, HbA1c and body mass index. HbA1c is a measure of average blood sugar over about three months. Another adult study found no link with body mass index (Zheng 2023).

None of this sets a dose. It explains why researchers study MOTS-c for metabolism. It does not show that giving MOTS-c to people restores anything.

Does a lab report confirm the MOTS-c peptide dosage in a vial?

No MOTS-c product is FDA-approved, so its quality depends on who made it. The FDA found MOTS-c is not well characterised, meaning its chemical make-up and quality are not well defined. It found no published quality-control data on its impurities, aggregates or endotoxins. Aggregates are clumps of peptide, and endotoxins are toxins from bacteria.

A certificate of analysis is a lab report on one batch. It can state how much peptide and how pure it is. Our guide on how to read a peptide COA shows what a real one looks like. Our guide on how to know if peptides are real covers the red flags. We keep a vendor-neutral list of what to look for on our recommended sources page. A test report shows what is in a vial. It does not show that MOTS-c is safe or that it works in people.

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References

Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. PubMed.

Lee C, et al. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. PubMed.

Kim SJ, et al. The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiological Reports.

Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. PMC PubMed.

Wan W, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. PMC PubMed.

Zheng Y, et al. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. PMC PubMed.

Pham T, et al. Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart. PMC PubMed.

Jia H, et al. Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane. PMC PubMed.

Kong BS, et al. Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes, Experimental & Molecular Medicine, 2025. Nature PubMed.

CohBar Announces Positive Topline Results from Phase 1a/1b Study of CB4211. GlobeNewswire.

ClinicalTrials.gov, NCT03998514: A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease. ClinicalTrials.gov.

FDA 2026, Briefing document for MOTS-c-related bulk drug substances, Pharmacy Compounding Advisory Committee, 23-24 July 2026. FDA.

This content is for educational purposes only and is not medical advice. Nothing here is a guide to research use or to treatment. A qualified clinician can advise on any health decision.