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MOTS-c Dosage: What Mouse and Human Studies Used, and Why No Dose Is Set

Every published MOTS-c dose was given to rodents. The only finished human trial used an analog and never posted its doses or results, so no human dose exists.

Article type
Safety
Sources
11
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5 min
By Leah GarnerPublished

People searching for a MOTS-c dosage are usually looking for a number to inject. There is no such number with evidence behind it. No study has given MOTS-c to people and reported the result.

What does exist is a set of mouse studies with specific doses, and two human trials whose doses are not public. This page sets out each one, with the species and route. What MOTS-c did in those studies is covered in MOTS-c evidence.

What MOTS-c is

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, first described in 2015 [1]. The body makes it naturally. In mice, its main target appeared to be skeletal muscle, where it activated AMPK, an energy-sensing enzyme.

The doses used in mice

The founding 2015 study gave MOTS-c by intraperitoneal injection, into the abdominal cavity, in every animal experiment [1]. Doses varied by experiment.

Mice given 5 mg/kg a day for 7 days cleared glucose faster and showed better insulin sensitivity. Mice on a high-fat diet given 0.5 mg/kg a day for 8 weeks gained less weight than untreated mice on the same diet [1].

A 2021 study from the same field tested physical capacity [2]. Young mice received 5 or 15 mg/kg a day for 2 weeks; on a high-fat diet, mice on the higher dose ran clearly better. Middle-aged and old mice received 15 mg/kg a day for 2 weeks and ran longer.

In the same study, mice starting at about 23.5 months of age received 15 mg/kg three times a week for the rest of life [2]. Grip strength and other physical measures were better than in untreated mice.

Every MOTS-c dose in this table was given to mice, by injection into the abdomen
StudyDose (mouse)DurationMeasured
Lee 20155 mg/kg/day7 daysGlucose clearance, insulin sensitivity
Lee 20150.5 mg/kg/day8 weeksWeight gain on high-fat diet
Reynolds 20215 or 15 mg/kg/day2 weeksTreadmill running
Reynolds 202115 mg/kg, 3 times a weekLate lifeGrip strength, physical capacity
Every MOTS-c dose in this table was given to mice, by injection into the abdomen

The human trials, and what they disclose

The one completed human trial tested CB4211, which a 2022 review describes as a MOTS-c analog [4]. An analog is a modified molecule, so its dose would not carry over to MOTS-c itself.

Its phase 1 trial enrolled 88 people and gave CB4211 by injection under the skin [5]. The registry lists the doses only as “Dose 1” through “Dose 6” and “Dose to be determined.” It was completed in April 2021, with no results posted.

A phase 2a trial of MOTS-c in adults with prediabetes and overweight or obesity began in February 2026 [6]. It gives a fixed dose once daily under the skin for 12 weeks, with 120 people planned. The registry does not state the dose, and its estimated completion date is May 2028.

What the body makes on its own

MOTS-c circulates in human blood without any injection. In 30 adults randomized to endurance exercise, resistance exercise or rest, MOTS-c levels showed only a trend toward rising after endurance exercise [3].

The 2021 mouse study also reported that exercise raised MOTS-c in human muscle and blood [2]. Those are natural levels. They say nothing about what an injected dose would do.

Regulatory and sport status

MOTS-c is on none of the FDA’s 503A category lists as of the May 14, 2026 update [8]. The FDA’s safety-risk page says it has found no human exposure data for MOTS-c by any route [9].

In July 2026 the FDA proposed not adding it to the 503A list [7]. The advisory committee voted to recommend adding it anyway [10]. That vote is not binding. The legal meaning of each list is in are peptides legal.

Athletes should know the 2026 World Anti-Doping Agency list names MOTS-c as a prohibited metabolic modulator at all times [11].

What this means

Any MOTS-c dose you see quoted for people is a guess. It may come from a mouse study, or from nowhere, but not from a human trial with published results. That could change when the phase 2a trial reports.

Epitalon, another peptide sold for aging, has a similar gap between claim and evidence; see epitalon. For longevity options with human data, start at the longevity goal page.

Frequently asked questions

What is the dosage of MOTS-c?
No human dose has been established or approved. Published doses come from rodent studies; the founding mouse studies injected 0.5 to 15 mg per kilogram into the abdomen, and the FDA noted that no study has worked out a dose-response relationship.
Has MOTS-c been tested in humans?
Not with published results. A phase 1 trial tested an analog, CB4211, and posted no results. A phase 2a trial of MOTS-c itself began in February 2026 and does not state its dose.
Is MOTS-c legal?
It is on no FDA 503A list, and the FDA proposed not adding it in July 2026. An advisory committee voted to recommend adding it, but that vote is not binding. It is banned at all times in sport.

Sources

11 cited
  1. 1Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance Cell Metabolism. PMID 25738459
  2. 2Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis Nature Communications. PMID 33473109
  3. 3von Walden F, Fernandez-Gonzalo R, Norrbom J, Emanuelsson EB, Figueiredo VC, Gidlund EK, et al. (2021). Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans Journal of Applied Physiology. PMID 34351816
  4. 4Miller B, Kim SJ, Kumagai H, Yen K, Cohen P (2022). Mitochondria-derived peptides in aging and healthspan Journal of Clinical Investigation. PMID 35499074
  5. 5CohBar, Inc. (2021). A Phase 1a/1b Study of Safety, Tolerability, and Pharmacokinetics of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease (NCT03998514) ClinicalTrials.gov. Source
  6. 6Hudson Biotech (2026). A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity (NCT07505745) ClinicalTrials.gov. Source
  7. 7U.S. Food and Drug Administration (2026). FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026 FDA. Source
  8. 8U.S. Food and Drug Administration (2026). Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (updated May 14, 2026) FDA. Source
  9. 9U.S. Food and Drug Administration (2026). Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks FDA, Human Drug Compounding (content current as of April 22, 2026). Source
  10. 10National Community Pharmacists Association (2026). FDA advisory committee nominates six peptides for pharmacies to compound NCPA (July 31, 2026). Source
  11. 11World Anti-Doping Agency (2026). World Anti-Doping Code International Standard: Prohibited List 2026 WADA. Source

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