MOTS-c Peptide: Benefits, Dosage Chart, Side Effects (2026)

MOTS-c: key takeaways

MOTS-c is a 16-amino-acid mitochondrial peptide with cell and mouse data on metabolism and exercise, no published human dosing study, and it is prohibited at all times in sport (WADA S4.4.1). Last reviewed: September 2026.

• First described in 2015, MOTS-c is encoded in a small open reading frame of the mitochondrial 12S rRNA gene (Lee 2015).
• In mice, doses of 0.5 to 15 mg/kg per day reduced diet-induced weight gain and insulin resistance and improved running performance (Lee 2015, Reynolds 2021).
• Human data cover the body's own MOTS-c: muscle levels rose 11.9-fold after cycling in 10 young men (Reynolds 2021).
• Reported use in forums and guides clusters around 5 to 15 mg per week, split into three injections or small daily doses.
• The first phase 2a trial, MOTS-MET (NCT07505745), started in February 2026 and has published no results.
• On the WADA 2026 and 2027 lists, MOTS-c is named under S4.4.1 (AMPK activators) and is banned at all times.

Jump directly to the dosage chart, reconstitution or side effects.

What is MOTS-c?

MOTS-c is a 16-amino-acid peptide encoded in a short open reading frame of the mitochondrial 12S rRNA gene and first described in 2015.

Its sequence is MRWQEMGYIFYPRKLR, the molecular formula C101H152N28O22S2 at 2,174.6 g/mol, and the CAS registry number 1627580-64-6. The structure is recorded in the PubChem entry for MOTS-c. Chemically it belongs to the mitochondrial-derived peptides, a class of peptides encoded by mitochondrial DNA.

Changhan Lee and Pinchas Cohen at the University of Southern California described MOTS-c in 2015; the intellectual property sits with UCLA and was licensed to CohBar, which developed the modified analog CB4211. Products sold as MOTS-c may be the free base, the acetate or the trifluoroacetate salt. There is no USAN or INN name, so the salt form can differ between suppliers.

How MOTS-c works

In cell and animal models, MOTS-c inhibits the folate cycle and de novo purine synthesis, which activates AMPK, while its exact molecular target remains unknown.

The 2015 study by Lee and colleagues identified skeletal muscle as a target tissue. In cells engineered to overproduce MOTS-c, endogenous AICAR accumulated to more than 20 times control levels, a cell-culture finding (HEK293 cells) without a matching animal or human result. Under glucose deprivation, MOTS-c moved into the cell nucleus in an AMPK-dependent way and regulated nuclear genes, including antioxidant response elements, with NRF2 involved (Kim 2018).

The FDA briefing document of May 2026 states that the molecular target of MOTS-c remains unknown, which makes organ-level effects hard to predict. A 2024 study reports that MOTS-c binds and activates the kinase CK2 in skeletal muscle: in mice there was less muscle atrophy and more glucose uptake in muscle, while the K14Q variant bound CK2 more weakly (Kumagai 2024). A 2026 eLife paper describes MOTS-c as an amphipathic host defense peptide with direct antibacterial activity that neutralized MRSA in a mouse peritonitis model (Rice 2026).

MOTS-c benefits and effects at a glance

Documented benefits come from cell and animal models and from observational blood levels, not from injecting MOTS-c in humans.

MOTS-c research and evidence

No published human study has tested MOTS-c administration: the evidence consists of cell and mouse studies, observational data on the body's own MOTS-c, phase 1 data on the analog CB4211 and one phase 2a trial still recruiting.

Animal studies: weight, metabolism and exercise

In mice, MOTS-c prevented diet-induced obesity and insulin resistance and improved running performance at doses of 0.5 to 15 mg/kg per day.

In the 2015 study by Lee and colleagues, male CD-1 mice on a high-fat diet received 0.5 mg/kg per day intraperitoneally for 8 weeks and weighed about 20 percent less than controls; in clamp experiments, 5 mg/kg per day for 7 days raised the glucose infusion rate by about 30 percent. The same paper reports that MOTS-c prevented age-related and diet-induced insulin resistance as well as diet-induced obesity.

Reynolds 2021 tested 5 and 15 mg/kg per day and found that only the higher dose improved running performance in young mice on a high-fat diet after 10 days; in middle-aged and old mice, 15 mg/kg per day for 2 weeks improved physical performance across age groups. Late-life dosing (15 mg/kg three times per week) showed only a trend toward longer life (median +6.4 percent, maximum +7.0 percent, P = 0.23).

In a separate study, the mtDNA variant m.1382A>C (K14Q) did not reproduce these effects in male mice on a high-fat diet, and female mice showed no effect at all (Zempo 2021). Male carriers of that variant also had type 2 diabetes more often in the cohorts analyzed.

Human data and the CB4211 analog

Human findings describe the body's own MOTS-c during exercise and in metabolic disease, and phase 1 tolerability of the analog CB4211, not effects of injected MOTS-c.

In 10 untrained young men who cycled on an ergometer, muscle MOTS-c rose 11.9-fold after exercise, blood levels rose 1.6-fold during and 1.5-fold after exercise, and both returned to baseline after 4 hours of rest (Reynolds 2021). In a randomized study (n = 30, 10 of them in the endurance group), plasma MOTS-c showed only a trend toward a rise after 45 minutes of endurance exercise (von Walden 2021).

Blood levels follow metabolic disease in observational studies. A meta-analysis of 7 studies (602 participants) found lower levels in type 2 diabetes (SMD -0.89) and higher levels in obesity (SMD +0.51) (Zhou 2024); a Qatari cross-sectional study also found lower levels in type 2 diabetes (Ramanjaneya 2019); one cross-sectional study reports 273 vs 223 pg/ml in adults with obesity and no change 6 months after bariatric surgery (Yoon 2026), another found no difference between obesity and normal weight (Ozkaya 2025), and children with obesity had lower levels (Luo 2023). Absolute values are not comparable between methods: one ELISA reported 45.9 to 218.5 ng/ml, which a validated mass spectrometry method could not confirm (Knoop 2019).

Only one human program in this class has reported results so far, and it tested an analog. In phase 1a, CB4211 was given as single and multiple ascending doses over one week to 65 healthy adults and was generally tolerated, with injection-site reactions the only event above 10 percent. In phase 1b, 20 adults with obesity and fatty liver received 25 mg once daily subcutaneously for 4 weeks (11 active, 9 placebo); ALT fell 21 percent vs 4 percent, AST 28 percent vs 11 percent and glucose 6 percent vs 0 percent, while liver fat (MRI-PDFF, -5.03 vs -4.88 percent) and body weight showed no clear advantage (CohBar topline release, August 10, 2021; NCT03998514). The release is a company statement, not a peer-reviewed paper.

For MOTS-c itself, the phase 2a study MOTS-MET (NCT07505745) plans 120 adults with prediabetes and overweight or obesity at one center (Shenzhen), a fixed dose once daily subcutaneously for 12 weeks (the amount is not published), with the Matsuda index as the primary endpoint. It started in February 2026, was listed as recruiting (registry last verified March 2026), and expects primary completion in February 2027.

MOTS-c dosage

There is no approved or study-validated human dose of MOTS-c: mice received 0.5 to 15 mg/kg per day, the analog CB4211 was given at 25 mg once daily, and reported use clusters around 5 to 15 mg per week.

Reported-use figures come from forum threads, a commercial clinic guide and supplier guide pages; they are not recommendations from a health authority. The chart comes first, then the doses from mouse and analog studies.

MOTS-c dosage chart: reported use

Reported use clusters around 5 to 15 mg per week, split either into three injections or into small daily doses, with a low start of 0.2 to 1 mg in forum reports.

Unit figures assume a 10 mg vial dissolved in 1 ml bacteriostatic water (10 mg/ml); the conversion is covered in the reconstitution section. For the math on any other vial size, use the peptide calculator.

Where those patterns come from:

• Peptide Critic forum, thread 1388 (10 users with dose data, posts from May 7 to June 18, 2026): 1 to 5 mg three times per week (most often 3.3 to 5 mg) or 0.2 to 2 mg daily; one user ran 5 mg on 4 to 5 days per week.
• Thread 1175 (April 21 and 22, 2026): 10 mg per week in 3 injections, 2.5 mg daily, 1.33 to 2 mg daily, or 1.5 to 2 mg every 3.5 days.
• Thread 349 (protocol post, author listed as a verified vendor): 200 mcg daily, increased by 200 mcg every 2 weeks up to 1 mg daily.
• Threads 2154 and 2273 (July 2026): 1 mg Monday to Friday over 12 weeks, 500 mcg, or about 1.5 mg daily.
• Healthspan clinic guide (June 29, 2026): start at 2.5 to 5 mg, then 5 to 10 mg per injection, 3 to 5 times per week.
• BergdorfBio calculator page: conservative start at 5 mg once weekly, standard 5 to 10 mg once or twice weekly.
• Path To Peptides: 5 to 10 mg per week on 1 to 3 days.

No clinical dose of MOTS-c exists. The range of 2.5 to 10 mg that some online guides call a clinical dose comes from clinic and forum practice, not from studies.

Dosage in studies (animal and analog)

Published dosing exists only for mice (0.5 to 15 mg/kg per day) and for the analog CB4211 (25 mg once daily in phase 1b).

Scaled by body surface area (FDA 2005 guidance), the mouse doses of 0.5, 5 and 15 mg/kg per day correspond to about 0.04, 0.41 and 1.22 mg/kg. This conversion does not establish an effective or safe human dose, and it ignores the injection route (i.p. in mice).

MOTS-c cycle and protocol

Reported cycles run 8 to 12 weeks followed by a 4 to 6 week break.

The two main patterns are a three-times-weekly schedule with weekly totals of 10 to 15 mg, and small daily doses that rise slowly. Forum reports often start at 0.2 to 1 mg to screen for allergic reactions, while the Healthspan clinic guide starts at 2.5 to 5 mg. Cycle length and the break figure mainly in guide pages (Healthspan: 8 to 12 weeks, then 4 to 6 weeks off; the BergdorfBio calculator: 8 to 12 weeks, then 4 weeks off; the vendor protocol post in thread 349: 8 to 12 weeks).

How to reconstitute MOTS-c

Add 1 ml of bacteriostatic water slowly down the side of a 10 mg vial, swirl until clear without shaking, and you get 10 mg/ml, so 10 units on a U-100 syringe hold 1 mg.

Reconstitution is one calculation chain: concentration (mg/ml) equals vial content (mg) divided by solvent (ml), volume (ml) equals dose (mg) divided by concentration, and units on a U-100 syringe equal volume (ml) times 100. Materials: a 10 mg MOTS-c 10 mg research vial, bacteriostatic water for injection (USP) and a U-100 insulin syringe.

How to mix MOTS-c

1. Work out the concentration: 10 mg in 1 ml gives 10 mg/ml. For other vial sizes use the peptide calculator.
2. Draw 1 ml bacteriostatic water and let it run slowly down the vial wall. Do not spray it onto the powder.
3. Swirl gently until the powder dissolves. Do not shake.
4. Check the solution for clarity, particles and discoloration before use.
5. Convert the dose: at 10 mg/ml, 5 mg is 0.5 ml (50 units), 2.5 mg is 0.25 ml (25 units) and 1 mg is 0.1 ml (10 units) on a U-100 syringe.
6. Keep the mixed vial at 2 to 8 °C and date it. BergdorfBio states 14 to 28 days after dissolving (supplier data).
7. Date the opened bacteriostatic water bottle and discard it after 28 days (label).

Store the unopened lyophilized vial frozen at minus 20 °C, dry and protected from light; short-term storage at 2 to 8 °C is possible. Besides the 10 mg vial, you may come across 5 mg vials (named in the FDA nomination) and 20 mg vials (Path To Peptides); for those sizes, enter the vial content in the peptide calculator.

BergdorfBio's product page suggests 2 ml of bacteriostatic water (5 mg/ml). With 2 ml, a 5 mg dose would be 1.0 ml (100 units) and fill a whole 1 ml syringe, which is why this guide uses 1 ml.

Reconstitution quick reference (U-100 units)

All rows assume a 10 mg vial dissolved in 1 ml bacteriostatic water (10 mg/ml) and show each dose on a U-100 and a U-40 syringe.

On a U-40 syringe the same unit count delivers 2.5 times the volume; check the U-100 print on the syringe, not the cap color (Barrera 2019). Peptide solutions are labeled in mg/ml, and the syringe marks are a volume scale.

How to inject MOTS-c

Use a short insulin syringe, always lift a skin fold, inject at 90 degrees and rotate sites.

These steps follow the FITTER 2016 and FIT UK 2019 injection recommendations, which were written for insulin and are applied here to subcutaneous research peptides.

1. Draw the dose into a U-100 insulin syringe. At 10 mg/ml, 1 mg is 10 units and 5 mg is 50 units.
2. Use the shortest available insulin syringe needle (the shortest syringe needles are 6 mm). Always lift a skin fold with a syringe, and with any needle longer than 4 mm.
3. If your BMI is under 19, the FIT UK recommendations advise against syringe needles altogether.
4. Inject at 90 degrees to the surface of the skin fold.
5. Keep the needle in the skin for at least 5 seconds after pressing the plunger (counting to 10 is better), then withdraw it at the same angle and release the fold.
6. Rotate sites: abdomen (about 2 cm from the navel), front and outer thigh, buttocks, and the back of the upper arm if someone else injects. Move each injection at least 1 cm from the previous one, and avoid scars, bruises and lipohypertrophy.
7. Use a new syringe and needle for every injection. If there is bleeding, press the site with gauze, do not rub.
8. Dispose of needles and syringes immediately in a puncture-proof container and follow local rules.

For general equipment, see injection supplies and injection accessories.

MOTS-c side effects

Human side-effect rates for MOTS-c are unknown; documented reports include histamine-like reactions and, for the analog CB4211, transient, mild to moderate injection-site reactions.

Without a human dosing study, there are no dose-related frequencies for MOTS-c itself. What is documented comes from the analog program, from authority notes and from user reports collected by USADA and in one forum, and from one commercial clinic guide.

Forum users start low because of the reported histamine-like and injection-site reactions. If you take glucose-lowering medicines, a clinic guide flags low blood sugar as a risk to watch. Seek medical advice for pronounced or persistent reactions, and get emergency help right away for signs of a severe allergic reaction such as trouble breathing, swelling of the face or throat, or fainting.

MOTS-c vs CB4211, AICAR and growth-hormone peptides

MOTS-c is a mitochondrial-derived peptide that activates AMPK through the folate cycle; CB4211 is its modified analog, AICAR and BAM15 are other AMPK activators in the same WADA subsection, and growth-hormone peptides such as tesamorelin, sermorelin, CJC-1295 and ipamorelin act on a different hormone axis.

Comparing these compounds matters because suppliers and forums group them loosely as "mitochondrial" or "metabolic" peptides. Mechanisms, evidence and prohibited-list entries differ.

Growth-hormone axis compounds such as tesamorelin share no documented mechanism with MOTS-c (see our tesamorelin dosing guide). Other mitochondrial-derived peptides such as SHLP2 have been measured alongside MOTS-c; in one study both were positively associated with liver fat in people without diabetes (Sequeira 2021). If you see MOTS-c sold alongside AICAR or BAM15, note that WADA names all three under the same subsection and that the compounds are not interchangeable.

Frequently asked questions

What is MOTS-c in simple terms?

MOTS-c is a mitochondrial peptide of 16 amino acids that circulates in the blood and rises in blood during exercise and in muscle after it. It was first described in 2015 by Lee and Cohen as a peptide encoded in the mitochondrial 12S rRNA gene. Most of what is known about it comes from cell and mouse studies.

What is the MOTS-c dosage?

Mouse studies used 0.5 to 15 mg/kg per day, and the analog CB4211 was tested at 25 mg once daily in phase 1b. In forums and guides, reported use is mostly 5 to 15 mg per week, split into three injections of 3.3 to 5 mg or into small daily doses. At 10 mg/ml, 3.3 to 5 mg equals 33 to 50 units on a U-100 syringe.

How do you reconstitute a 10 mg MOTS-c vial?

Let 1 ml of bacteriostatic water run down the vial wall and swirl without shaking. The concentration is 10 mg/ml: 5 mg equals 0.5 ml or 50 units, 2.5 mg equals 25 units, 1 mg equals 10 units on a U-100 syringe. The supplier's product page suggests 2 ml instead (5 mg/ml), which would make 5 mg fill a 1 ml syringe; this guide uses 1 ml.

How much MOTS-c do people inject per day?

Forum reports describe 0.2 to 2 mg per day, often with a low start of 0.2 to 1 mg to screen for allergic reactions. Other users do not inject daily but split a weekly total of 10 to 15 mg into three injections. One vendor protocol post starts at 200 mcg daily and steps up to 1 mg over several weeks.

What is a typical MOTS-c protocol or cycle?

Two patterns dominate: three injections per week (10 to 15 mg weekly) or small daily doses that rise slowly. Forum reports start as low as 0.2 to 1 mg, while the Healthspan clinic guide starts at 2.5 to 5 mg. Guides describe 8 to 12 weeks of use, then a 4 to 6 week break before the next cycle.

What benefits does MOTS-c show in research?

In mice, MOTS-c supported insulin sensitivity, body-weight control and running performance in the studies by Lee 2015 and Reynolds 2021. Human data describe the body's own MOTS-c: levels rise in muscle and blood after exercise and are often lower in type 2 diabetes. One modified analog, CB4211, completed a phase 1 program; MOTS-c itself has no published administration study.

What side effects are reported for MOTS-c?

Forum reports describe histamine-like and allergic reactions, which is why many users start at 0.2 to 1 mg. In the phase 1 program with the analog CB4211, the only event above 10 percent was transient, mild to moderate injection-site reactions. The FDA notes possible immunogenicity from aggregates and peptide-related impurities in compounded products.

What do MOTS-c before and after results show?

No published before-and-after study has tested MOTS-c in people. The often cited figure, about 20 percent less body weight after 8 weeks, comes from male mice on a high-fat diet in the 2015 Lee study. User photos and reports in forums are anecdote and cannot show what the peptide does in humans.

What do Reddit and forum users report about MOTS-c?

The reports reviewed for this guide come from the Peptide Critic forum (about 17 users in 5 threads), not from a systematic look at Reddit. They describe histamine-like reactions, injection-site reactions and dosing from 0.2 mg daily up to 5 mg on 4 to 5 days per week. One protocol post comes from a verified vendor.

How long does MOTS-c stay in the body?

No pharmacokinetic study of MOTS-c in people or animals has been published, so the half-life of an injected dose is unknown. In human whole blood in the lab, MOTS-c is quickly broken down into shorter fragments. That lab result does not show how long an injected dose stays active in the body.

Sources

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6. Rice MC et al.: MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide. eLife 2026. PMID 42611943.
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