Summary
- What it does
- MOTS-c is used for better blood sugar and for fitness gains like those from exercise. It has no approved human use.
- How it works
- A short peptide written in the DNA of mitochondria, the parts of cells that make energy. It is given as an injection under the skin. It switches on AMPK, the cell's energy sensor, and is thought to copy some of the changes that exercise brings.
- WADA status
- Prohibited by the World Anti-Doping Agency (WADA). Drug-tested athletes cannot use it.
MOTS-c (also known as Mitochondrial ORF of the 12S rRNA type-c) is a peptide studied for its effects on metabolic health, fat loss, and aging. Mitochondrial peptide activating AMPK to boost insulin sensitivity and mimic exercise adaptations. Investigational, WADA-prohibited, preclinical evidence only.
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial genome rather than the nuclear DNA. It functions as a regulator of metabolic homeostasis: under metabolic stress such as glucose restriction or exercise, MOTS-c translocates from the cytoplasm to the nucleus, where it helps direct an adaptive antioxidant and metabolic stress response, in part through activation of AMP-activated protein kinase (AMPK). In cell and rodent models it enhances glucose uptake and insulin sensitivity, improves lipid metabolism, reduces diet-induced obesity, and reproduces and amplifies several of the metabolic adaptations normally produced by physical exercise, leading some researchers to describe it as an 'exercise-mimetic' peptide.
Overview
Circulating MOTS-c levels decline with age and are altered in metabolic disease.
MOTS-c is an investigational research peptide with no approved human indication, and it is banned by the World Anti-Doping Agency (WADA) as a prohibited metabolic modulator, explicitly named as an AMP-activated protein kinase (AMPK) activator under category S4.4.1 and banned at all times, in and out of competition, since the 2025 Prohibited List.
Human data are largely limited to observational associations between endogenous MOTS-c levels and fitness or metabolic status; demonstrated efficacy comes from preclinical cell and animal experiments, not controlled human trials.
Mechanism of action
Mitochondrial-derived peptide that activates AMPK to improve insulin sensitivity and reproduce exercise-like metabolic adaptations in preclinical models. Investigational and WADA-banned; no approved human use.
Reported effects
Effects reported in the literature and from preclinical models include:
- MOTS-c alleviated hyperglycemia and improved insulin sensitivity and glucose tolerance in a mouse model of gestational diabetes. [2] Preclinical
- MOTS-c protected pancreatic beta-cells from streptozotocin-induced injury and reduced the offspring death caused by gestational diabetes in mice. [2] Preclinical
- Systemic MOTS-c administration increased exercise performance by boosting skeletal muscle stress responses and enhancing metabolic adaptation to exercise. [3] Preclinical
- Exogenous MOTS-c stimulated thermogenesis in subcutaneous white adipose tissue, which increased energy expenditure and contributed to the anti-obesity effects of exercise training. [3] Preclinical
- Under glucose restriction, MOTS-c translocated to the nucleus and regulated antioxidant response element genes in an AMPK-dependent manner, interacting with the stress-responsive transcription factor NRF2. [1] Preclinical
- Exogenous MOTS-c administration attenuated lung injury in preclinical models of acute respiratory distress. [4][5] Preclinical
Evidence grades: FDA approvedApproved (non-US)Phase IIIPhase IIPhase IPreclinicalAnecdotal
Dosage and administration
General
- Investigational research peptide with no established or approved human dose
- Rodent studies use intraperitoneal dosing in the 0.5-15 mg/kg range
- Human interventional dosing has not been validated in controlled trials
Natty status
MOTS-c is classified as not natty. It appears on the WADA prohibited list and is banned by major natural bodybuilding federations.[6] Use of this compound places the athlete in the enhanced category rather than the natural category in competitive contexts.
Research
The peptide has been the subject of 12 studies and reference works collected on this site. Additional bibliography is in § External links below.
Related compounds
Other peptides in this catalogue with overlapping mechanisms or status:
Frequently asked questions
What is MOTS-c?
Mitochondrial peptide activating AMPK to boost insulin sensitivity and mimic exercise adaptations. Investigational, WADA-prohibited, preclinical evidence only.
What is MOTS-c used for?
MOTS-c is used for better blood sugar and for fitness gains like those from exercise. It has no approved human use.
How does MOTS-c work?
A short peptide written in the DNA of mitochondria, the parts of cells that make energy. It is given as an injection under the skin. It switches on AMPK, the cell's energy sensor, and is thought to copy some of the changes that exercise brings.
Is MOTS-c natty?
No. MOTS-c is classified as not natty. It is prohibited by WADA and banned by most natural bodybuilding federations. Use places an athlete in the enhanced category.
Is MOTS-c banned by WADA?
Yes. MOTS-c is prohibited by the World Anti-Doping Agency (WADA), so drug-tested athletes cannot use it. Check the current WADA Prohibited List before competing.
How is MOTS-c administered?
MOTS-c is typically administered via: subcutaneous injection. Dosage and administration protocols vary; see the Dosage section for details.
References
- ^ The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Metabolic Homeostasis (Cell Metab 2018)
- a b MOTS-c relieves hyperglycemia and insulin resistance (preclinical, Pharmacol Res 2022)
- a b Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) (review, Diabetes Metab J 2022) Recent
- ^ MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases. Recent review
- ^ Mitochondrial dysfunction in ARDS: unraveling the regulatory networks and therapeutic opportunities. Recent review
- a b World Anti-Doping Agency. (2026). Prohibited List 2026.
External links
- Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.
- Wikipedia article
- Emerging regulators of human physiology and disease; sORF-encoded microproteins.
- Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review.
- MOTS-c in sepsis-induced cardiomyopathy: Mechanisms and translational potential.
- Synthetic Peptides in Pharmacy Compounding: Analysis of PCAC Recommendations and Industry Safety Standards.
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.
- 10mg MOTS-c — commercial
This page was last updated on October 5, 2026, at 07:26 (UTC).
Research last reviewed on October 5, 2026.
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