What The 'Exercise In A Bottle' Peptide Actually Does To Your Metabolism

Unless you've been living under a rock for the past five years, you've probably heard the word "peptide" tossed around, most likely in the context of weight-loss drugs like semaglutide, which mimics a natural peptide relating to satiety, although it, like Ozempic, has long-term consequences to be aware of.  Recently, MOTS-c, a peptide discovered in 2015, has been gaining popularity for a supposed host of metabolic- and exercise-related benefits, to the point that it's commonly called "exercise in a bottle." There is some truth to these claims, but there's just as much we don't know about the health effects of MOTS-c than what we do know.

MOTS-c (Mitochondrial Open reading frame of the 12S [Twelve S] rRNA type-c) is unique among peptides because it's one of the few known to be produced by mitochondrial DNA. It's released from the mitochondria into the cellular cytoplasm when you exercise (among other things) and triggers a cascade of chemical reactions, ultimately leading to more adenosine monophosphate–activated protein kinase (AMPK) production. 

AMPK has myriad functions throughout the body, but it's most well known for increasing how much fat you burn and how much sugar your muscles take from the blood. Nearly all of the lauded benefits of MOTS-c stem from its buff to AMPK production.

When you look around online for information on MOTS-c, you'll see lots of health claims, like it can burn fat, give you more energy, or even reduce the signs of aging. For the most part, there is a grain of truth to these claims (the kind of thing which could lead to peptides being greenlit by the FDA), but there's also a good bit of nuance, so don't take all of these claims at face value. The most important thing to keep in mind is that nearly all studies involving MOTS-c so far have been conducted on rodents, and of the human studies, only endogenous MOTS-c levels have been analyzed in published research, not the effects of injected MOTS-c.

Many of MOTS-c's touted benefits are elucidated in the foundational 2015 Cell Metabolism paper. The study authors tested MOTS-c in both cells and living mice. The authors found that MOTS-c targets skeletal muscles and improves their insulin sensitivity, helping them to consume more glucose. At the same time, it prevented obesity in rats fed a high-fat diet. MOTS-c also temporarily restored insulin sensitivity in aged mice to levels seen in young mice.

Additionally, MOTS-c may even confer short-term improvements to your strength and endurance. A 2022 study in Physiological Reports tested the physical performance of rats after MOTS-c injection. It found that after just one injection of MOTS-c, the rats ran longer and for greater distance. Another study found improved cardiac function in rats after exercise and MOTS-c administration, a greater improvement than the rat cohort that exercised without MOTS-c.

One thing to remember about MOTS-c is that it has not been approved for human use by any national regulatory agency. Further, organizations like the U.S. Anti-Doping Agency actively ban MOTS-c. The only way to get your hands on it is through grey market vendors that aren't held to any legal standards of purity. In fact, there are stories of people going to the emergency room thanks to shoddy batches of MOTS-c, so think twice before injecting sketchy peptides.

And when it comes to human testing, hardly anything is known. A MOTS-c analog (CB4211) was developed and tested a few years ago, but all testing on it was abandoned. According to an SEC filing from CohBar, the company developing CB4211, it ceased work on the drug after it couldn't resolve problems with the drug's injection. The filing is explicit: "We do not believe that the formulation of CB4211 used in the Phase 1b stage of the trial is suitable for further development."

That said, there is at least one study in the works, but it's not investigating the "exercise in a bottle" effects. Instead, it's a phase 2 study (a study that will test efficacy) looking into whether MOTS-c can improve insulin sensitivity in prediabetic and overweight adults over the course of 16 weeks. Improved insulin sensitivity has already been established in murine models (rodent testing), but this will be one of the first to look at how MOTS-c affects human patients. Long story short: We are in the early days of MOTS-c testing and we still have a long way to go before we understand how supplementing with it will affect our health.