MOTS-c is a 16-amino-acid peptide made by mitochondria, the energy factories inside cells. In mice it protected against diet-induced obesity and insulin resistance and improved physical performance.[1][3] FDA says it has found no clinical studies or human exposure data for MOTS-c by any route, and it is not FDA-approved.[4]
This profile covers how MOTS-c works, what animal and human research shows, side effects, doses used in studies, and its FDA and anti-doping status.
What is MOTS-c?
MOTS-c stands for “mitochondrial open reading frame of the 12S rRNA type-c”. Researchers at the University of Southern California discovered it in 2015, hidden in a stretch of mitochondrial DNA. It circulates in human and rodent blood, and its main target appears to be skeletal muscle.[1]
It belongs to a small family of “mitochondrial-derived peptides”, signals that let mitochondria communicate with the rest of the body.
How MOTS-c works
In the discovery study, MOTS-c disrupted a cell pathway called the folate cycle, which switched on AMPK, a master energy sensor that also responds to exercise.[1] When cells are under metabolic stress, MOTS-c moves into the nucleus and helps switch on protective genes.[2]
FDA’s 2026 review cautions that the exact molecules MOTS-c binds to are still unknown, and that human blood breaks MOTS-c down quickly in the lab, which raises questions about whether injected MOTS-c reaches active levels.[4][17]
MOTS-c benefits: what the research shows
In animals
- Obesity and blood sugar: mice on a high-fat diet given MOTS-c for 8 weeks weighed about 20% less than untreated mice and stayed insulin-sensitive.[1][4]
- Exercise and aging: MOTS-c improved running performance in young, middle-aged and old mice. Treatment started late in life improved grip strength and walking, but the increase in lifespan was not statistically significant.[3]
- Autoimmune diabetes: in a Korean study, MOTS-c protected mice from the immune attack that causes type 1 diabetes.[19]
In people
There are no published human trials of MOTS-c itself.[4] The human evidence comes from measuring the body’s own MOTS-c:
- Exercise raises it. In 10 young men, a cycling session raised MOTS-c 11.9-fold in muscle and about 1.5-fold in blood.[3]
- Blood levels fall with age, although muscle levels were higher in older men.[16]
- Links to metabolism are inconsistent. One study found no difference between lean and obese people.[18] Across three cohorts totaling 27,527 people, men (but not women) carrying an East Asian variant of the MOTS-c gene had higher rates of type 2 diabetes.[15]
- Measurement is unreliable. Reported blood levels vary widely depending on the lab test used.[17]
The CB4211 trial
CohBar, the company that licensed MOTS-c, developed an improved analog called CB4211. In a phase 1b trial in 20 adults with obesity and fatty liver disease, 25 mg daily for 4 weeks lowered the liver enzyme ALT by 21% versus a 4% rise with placebo, and modestly lowered blood sugar. However, liver fat fell by a similar amount in both groups.[6] In 2023 the company said the formulation was not suitable for further development, and it later moved to dissolve itself.[7]
MOTS-c research around the world
Much of the newer MOTS-c research comes from outside the United States. All of it measures natural MOTS-c levels in people, or tests it in animals:
- China: higher blood MOTS-c predicted heart attack and unstable angina in 400 patients with acute coronary syndrome[20], and marathon runners had MOTS-c levels that tracked with aerobic fitness[21].
- Japan: a MOTS-c gene variant was more common in sprint and power athletes and was linked to more fast-twitch muscle fiber.[22]
- Türkiye: people with fatty liver disease had lower MOTS-c than healthy controls.[23]
- Italy: MOTS-c levels predicted death and heart risk in people on hemodialysis.[24]
- Korea: MOTS-c prevented autoimmune diabetes in mice, and people with type 1 diabetes had lower levels.[19]
We did not find published Russian-language research on MOTS-c.
MOTS-c side effects and safety
- MOTS-c itself: side effects in humans are unknown. FDA found no adverse event reports in its database and no animal toxicity studies.[4]
- CB4211 (analog): no serious adverse events. The only side effects in more than 10% of people were temporary, mostly mild to moderate injection-site reactions.[6]
- FDA’s concerns: possible immune reactions from clumped peptide or impurities, and confusion between the “free base” and “acetate” forms sold.[4][10]
MOTS-c dosage: what has been studied
No dose of MOTS-c has been established or tested for safety in people. FDA notes that dose-response studies are missing.[4]
| Setting | Dose |
|---|---|
| CB4211 analog, phase 1b | 25 mg under the skin once daily for 4 weeks[6] |
| Mouse obesity study | 0.5 mg per kg per day[1] |
| Mouse exercise study | 5 to 15 mg per kg per day[3] |
| Compounding nomination (withdrawn) | 5 mg and 10 mg injections proposed[4] |
Mouse doses cannot be converted directly into a human dose. For vial math, see our peptide calculator.
Is MOTS-c FDA approved or legal?
- Not FDA-approved. MOTS-c is not part of any approved drug.[4]
- Compounding: FDA placed MOTS-c on its list of substances with possible significant safety risks in 2023. After the nomination was withdrawn, FDA reviewed it on its own and recommended against allowing it in compounding.[5][10]
- July 2026 advisory vote: FDA’s Pharmacy Compounding Advisory Committee reviewed MOTS-c for obesity and osteoporosis.[11] According to news reports, the committee voted 7 to 5 to recommend it, against FDA scientists’ advice. The vote is not binding, and MOTS-c had not been added to the list as of our last review.[12]
- Banned in sport. The World Anti-Doping Agency lists MOTS-c as a prohibited AMPK activator, banned at all times.[13] USADA says an exemption for athletes is highly unlikely.[14]
This is general information, not legal advice.
MOTS-c vs NAD+
MOTS-c and NAD+ are both sold for energy and healthy aging, and are often stacked. MOTS-c is a peptide signal from mitochondria, while NAD+ is a coenzyme that cells use in energy reactions. NAD+ precursors have been tested in dozens of human trials; MOTS-c has none published yet. Neither has been shown to slow aging in people.