What is the MOTS-c peptide?

What is MOTS-c?

Athletes should be extremely cautious about experimental peptides, including the prohibited peptide MOTS-c, which is often marketed online with the label “for research purposes only.” Below, we explore the health and anti-doping risks associated with MOTS-c.

What is MOTS-c?

MOTS-c is a 16-amino acid peptide encoded by the mitochondrial genome. Mitochondria are the "power generators" in cells, converting chemical energy from food into a usable form for cellular functions. Alongside MOTS-c, two other mitochondrial-derived peptides (MDPs)—humanin and SHLP1-6—have been identified, though their potential role in human performance enhancement remains unclear. Recent research suggests that mitochondrial-derived peptides like MOTS-c play a role in maintaining mitochondrial function and protecting cells under various stressors (Reynolds et al., 2021). Studies have shown that exercise increases MOTS-c levels in humans. Additionally, in mice, MOTS-c treatment has been found to enhance physical performance across all ages and appears to regulate skeletal muscle metabolism and gene expression (Reynolds et al., 2021).

Are there medical uses for MOTS-c?

No, MOTS-c is still an experimental peptide and is being investigated for potential therapeutic applications related to aging and obesity. It is not approved by the U.S. Food and Drug Administration (FDA) for human use. The FDA has also clarified that MOTS-c is among the substances that cannot legally be used in compounded medications (FDA, 2023). This means compounding pharmacies, which custom-mix medications, are prohibited from using MOTS-c in their formulations.

Is MOTS-c prohibited in sport?

Yes, MOTS-c is prohibited at all times under Section 4.4 (Metabolic Modulators) and specifically under 4.4.1 (Activators of the AMP-activated protein kinase (AMPK)) on the World Anti-Doping Agency (WADA) Prohibited List.

Can athletes get a Therapeutic Use Exemption (TUE) for MOTS-c?

No, athletes cannot obtain a TUE for MOTS-c because it has no approved therapeutic use.

Is MOTS-c used in dietary supplements?

No, MOTS-c is not recognized as a legitimate dietary ingredient and cannot legally be included in dietary supplements.

Is MOTS-c available online?

Yes, MOTS-c is advertised on many websites as an injectable peptide for weight loss and bodybuilding, often labeled “for research purposes only.” However, its availability online does not mean it is safe or legal. The FDA faces significant challenges in regulating the online sale of such products, as there are no direct laws prohibiting or supporting these sales. Despite this, many individuals on social media claim to purchase and use MOTS-c for weight loss or muscle building. Athletes are strongly advised against purchasing or using any product sold with this disclaimer.

Is MOTS-c safe to use?

The safety of MOTS-c remains unknown, as no clinical trials have been completed to determine its safety or appropriate usage conditions. However, individuals who claim to have purchased MOTS-c online report side effects such as increased heart rate, heart palpitations, injection site irritation, insomnia, and fever. There is also no data on the long-term effects of MOTS-c use.

References

Reynolds, J. C., Lai, R. W., Woodhead, J. S. T., Joly, J. H., Mitchell, C. J., Cameron-Smith, D., Lu, R., Cohen, P., Graham, N. A., Benayoun, B. A., & Lee, C. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications, 12(1), 470. https://doi.org/10.1038/s41467-020-20790-0

U.S. Food and Drug Administration (FDA). (2023). Safety Risks Associated with Certain Bulk Drug Substances Nominated for Use in Compounding. Retrieved from https://www.fda.gov/drugs/human-drug-compounding/safety-risks-associated-certain-bulk-drug-substances-nominated-use-compounding