Metabolic & weight

MOTS-c

Also called mitochondrial open reading frame of the 12S rRNA-c, MOTSc, CB4211 (related analog)

MOTS-c is a small peptide made from instructions in mitochondrial DNA, the cell's 'power plant' genes. In mice it improved insulin sensitivity, prevented diet-induced weight gain, and boosted exercise capacity. There are no published human treatment trials of MOTS-c itself.

Preclinical onlyStudied in cells or animals only. Effects in people are unknown.

All printable flashcards

Drawn from its published sequence: 16 residues, one bead each.

Overview

How it works

Proposed, mostly from mouse and cell studies: MOTS-c acts mainly on skeletal muscle. It interferes with the folate cycle, which raises the level of a natural molecule (AICAR) that activates AMPK, a cellular energy sensor. This improves glucose uptake and insulin sensitivity. Under stress it can move into the cell nucleus and affect gene activity. These effects have not been confirmed in human treatment studies.

What research shows

Mouse studies (Lee et al., Cell Metabolism 2015): MOTS-c injections prevented high-fat-diet obesity and insulin resistance and reversed age-related insulin resistance.
Human exercise study (n=10 sedentary young men): exercise raised muscle MOTS-c about 12-fold and blood levels about 1.5-fold (observational, no MOTS-c given).
Old mice treated with MOTS-c ran longer and farther, and late-life treatment improved grip strength and walking; lifespan effect not significant.
Related analog CB4211 (phase 1b RCT, n=20 obese adults with fatty liver, 4 weeks): lowered liver enzymes and glucose vs placebo; not the same molecule as MOTS-c.

Doses studied in people

No published human dosing data for MOTS-c itself; doses circulating online are extrapolated from animal studies. (A related analog, CB4211, was tested at 25 mg daily in a small 4-week phase 1b trial.)

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Weekly protocol

How the schedule looks week by week. Each chart says where it comes from: a prescribing label, a clinical trial, or a protocol commonly reported online.

PeptideDosages.com titration model

Commonly reported, not studied

One week

D1D2D3D4D5D6D7

Once daily · Subcutaneous injection

Syringe units (U-100)

Vial Water added

Dose by week

200 mcgwk 1–2

400 mcgwk 3–4

600 mcgwk 5–6

800 mcgwk 7–8

1,000 mcgwk 9+

Course: About 10 weeks; supply tables cover 8–16 weeks
Note: The site calls this a calculation model, not a validated human schedule. No human trial has tested MOTS-c itself.
Source: PeptideDosages.com: MOTS-C (10 mg vial) dosage protocol
Also: PepDex: MOTS-c

Higher-dose intermittent protocol

Commonly reported, not studied

One week

D1D2D3D4D5D6D7

Two to three times weekly (or every 5 days) · Subcutaneous injection

Syringe units (U-100)

Vial Water added

Dose by week

5–10 mg per injectionwk 1–6

Supplies for one course (estimate)

Counts only. This site does not sell or link to supplies.

Course: 4–6 weeks, repeated 2–4 times a year
Note: A very different pattern from the daily microgram model above; neither comes from human data.
Source: Peptide Protocol Wiki: MOTS-c dosing protocols

Reference only, not a recommendation. Charts marked "commonly reported" describe what public sources say people use. They have not been tested in trials, and their safety and effect are unknown. Label and trial schedules were set for specific patients under medical supervision. Use the calculator only to understand the arithmetic.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

Vial	Liquid added	Concentration	Per unit (0.01 mL)
5 mg	1 mL	5 mg/mL	50 mcg	Open in calculator
5 mg	2 mL	2.5 mg/mL	25 mcg	Open in calculator
5 mg	3 mL	1.67 mg/mL	16.7 mcg	Open in calculator
10 mg	1 mL	10 mg/mL	100 mcg	Open in calculator
10 mg	2 mL	5 mg/mL	50 mcg	Open in calculator
10 mg	3 mL	3.33 mg/mL	33.3 mcg	Open in calculator

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

FDA says it has not identified any human exposure data for MOTS-c and lacks important safety information.
CB4211, a related analog, showed only mild-to-moderate injection-site reactions in a 4-week, 20-person trial; this does not establish MOTS-c safety.
Unknown long-term safety; product purity from research-chemical sellers is unverified.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA: Not FDA-approved for any use.
Compounding: Removed from FDA's 503A Category 2 list in April 2026 and moved to 'nominated but withdrawn'; not placed on Category 1, so not yet lawful to compound. Reviewed by the Pharmacy Compounding Advisory Committee on July 23, 2026 (for obesity and osteoporosis); outcome and any final FDA action not verified — check current status. Any addition to the 503A bulks list would require rulemaking. Update: on October 28, 2026 HHS issued an interim enforcement discretion policy covering MOTS-c: HHS does not intend to take action against 503A pharmacies, federal facilities or physicians that compound it under set conditions (patient-specific prescription, FDA-registered ingredient source with a certificate of analysis, single ingredient, adverse-event reporting), limited to injection under the skin or into muscle. This is not FDA approval, is non-binding, and applies only until a final rule on the 503A bulks list ⁹¹⁰.
Sports (WADA): Prohibited at all times: listed by name under S4.4.1 (metabolic modulators, AMPK activators) since 2024.
Other: Not a controlled substance.

Rules change often. See Legal status of peptides for how these categories work.

History

Discovered by Changhan Lee, Pinchas Cohen and colleagues at USC and reported in Cell Metabolism in 2015. A 2021 Nature Communications study showed exercise raises MOTS-c in human muscle and blood, and treatment improved physical performance in old mice. CohBar developed a related analog, CB4211, which completed a small phase 1b trial in 2021. WADA added MOTS-c to its Prohibited List in 2024. FDA placed it on its compounding Category 2 list in 2023, removed it in April 2026, and scheduled it for advisory committee review on July 23, 2026.

Common questions

Is MOTS-c FDA-approved?

No. It is not approved for any use ⁵. FDA removed it from its compounding safety-risk list in April 2026 without clearing it for compounding, and an FDA advisory committee reviewed it on July 23, 2026 ⁵⁶⁷. Update: on October 28, 2026 HHS issued an interim, non-binding policy saying it does not intend to take action against licensed pharmacies, federal facilities or physicians that compound MOTS-c under set conditions, including a patient-specific prescription. This is not FDA approval, and it applies only until a final rule on the 503A bulks list ⁹¹⁰.

What does the research show?

In mice, MOTS-c injections prevented weight gain and insulin resistance on a high-fat diet ¹. Old mice given it ran longer and farther and had better grip strength ³. No published human treatment trials of MOTS-c itself exist.

Does exercise raise MOTS-c levels?

In a small study of 10 inactive young men, exercise raised MOTS-c about 12-fold in muscle and about 1.5-fold in blood ³. No MOTS-c was given in that study ³.

What doses were studied in people?

None. FDA says it has found no human exposure data for MOTS-c, so doses seen online are extrapolated from animal studies ⁵. A related but different molecule, CB4211, was tested at 25 mg daily in a small 4-week trial ⁴.

Is MOTS-c safe?

FDA says it lacks important safety information on MOTS-c ⁵. The related analog CB4211 caused mild-to-moderate injection-site reactions in a 20-person trial, but that does not show MOTS-c itself is safe ⁴.

Is MOTS-c banned in sport?

Yes. Since 2024, WADA has listed it by name as a metabolic modulator that is prohibited at all times ⁸.

Related compounds

Metabolic & weightEarly human dataFlashcard

AOD-9604

AOD9604 · Tyr-hGH 177-191

AOD-9604 is a small piece of human growth hormone that was developed in Australia as a fat-loss drug.

Longevity & mitochondrialPreclinical onlyFlashcard

Humanin

HN · HNG (S14G analogue)

Humanin is a small peptide made from genetic code inside the mitochondria.

Longevity & mitochondrialFDA-approvedFlashcard

SS-31 (elamipretide)

elamipretide · Forzinity

SS-31, now called elamipretide, is a small lab-made peptide that travels to the mitochondria, the cell's power plants.

Sources

Last reviewed 2026-10-29 · How we research · Found an error? See our corrections policy.