MOTS-c Peptide: Benefits, side effects, dosage details, and how it works

Peptides aren’t only for people who want to lose weight or gain muscle. Many offer an array of therapeutic benefits targeting diverse health concerns, including the aging process itself. That’s certainly the case with MOTS-c, a peptide derived from mitochondrial DNA.

In this guide, we discuss what MOTS-c does, how it works, and its current pharmaceutical status. Along the way, we’ll touch on other relevant points to familiarize you with this treatment.

Over the past two decades, Innerbody Research has helped tens of millions of readers make more informed decisions about staying healthy and living healthier lifestyles.

MOTS-c is part of our ongoing exploration of peptide therapies, in which we’ve cumulatively dedicated more than 700 hours to date. After studying hundreds of sources in scientific and medical journals and consulting with medical professionals on peptide uses, we’re able to offer a uniquely multifaceted perspective. Also, our relationships with healthcare providers familiar with the peptide and our firsthand knowledge of similar drugs allow us to present the lowest-altitude view of the subject that’s currently possible.

Additionally, like all health-related content on this website, this guide was thoroughly vetted by one or more members of our Medical Review Board for accuracy, and our editorial team will continue to monitor it for updates.

MOTS-c is a naturally occurring protein hormone and experimental therapeutic peptide comprising 16 amino acids. Its name is short for “mitochondrial ORF of the 12S rRNA type-C,” which refers to the peptide’s origin, as it’s derived from lengths of DNA called short open-reading frames (ORFs) found in the 12S rRNA region of mitochondrial DNA.1 2

Because MOTS-c’s mitochondrial origin is pivotal to understanding what the peptide can do for you and how it works, we think now’s a good time for a mitochondria primer.

Why mitochondria matter

As you might recall from your high school biology textbook, mitochondria are considered the powerhouses of the cell due to their role as energy suppliers, intercellular signalers, and metabolic coordinators.3 As such, they’re central to a biological process called apoptosis (cell death), which involves the disposal of damaged or abnormal cells.4 Also, apart from the nucleus, mitochondria are the only other parts of a human cell that carry DNA.5 Therefore, mitochondrial dysfunction is inextricably linked to health conditions stemming from cellular breakdown and chromosomal changes, both of which correlate with aging.6 7 Apart from primary mitochondrial diseases such as Leigh syndrome and MELAS syndrome, these health conditions include but aren’t limited to:8 9 10

• Cancer
• Diabetes
• Heart disease
• Kidney diseases
• Neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s)
• Hearing loss
• Eyesight abnormalities
• Oxidative stress
• Metabolic imbalance
• Inflammation
• Myalgic encephalomyelitis, or ME/CFS (potentially; more research is needed)50

Think of MOTS-c as a cellular ambassador whose efforts make possible the working relations between numerous biological processes.

As a naturally occurring protein hormone, MOTS-c is primarily activated by exercise or some type of stress, whereupon it translocates to the cell’s nucleus and mediates mitochondrial-nuclear communication.11 This crosstalk is crucial for coordinating the many mitochondrial functions and maintaining homeostasis.12 MOTS-c also activates the AMP-activated protein kinase (AMPK) pathway, a key regulator of cellular metabolism and homeostasis that helps produce energy by stimulating glucose uptake and fat oxidation.13 Much of this activity takes place in the skeletal muscles, which are rich in mitochondria because of their high energy demand.14

Over time, however, MOTS-c loses influence because its concentration declines with age.11 Consequently, people can become increasingly susceptible to some of the health conditions we listed in the previous section, many of which you may have noticed are largely age-correlated. But as a therapeutic peptide, MOTS-c is supplemental: it fills the vacancy and ensures healthy ongoing interrelations in the body’s biochemistry.

With its combined effects on cellular metabolism, stress response, and longevity, MOTS-c has many of the same therapeutic uses as growth hormone secretagogues (substances that stimulate growth hormone secretion) such as CJC-1295, ipamorelin, and tesamorelin. Most of the clinical research has been conducted in rodent models, with a few human studies here and there, but the biological similarities between rodents and humans present a promising picture of how MOTS-c might impart the following health benefits:15

MOTS-c’s diverse therapeutic effects may help users realize numerous downstream health effects:

• Diabetes: Inefficient glucose uptake is a characteristic of type 2 diabetes, and mitochondrial dysfunction may result in two risk factors for the disease — insulin resistance and impaired insulin secretion.32 33 MOTS-c’s actions on these risk factors may help nip them in the bud.34
• Cardiovascular health: Diabetes is a cardiovascular risk factor, so cutting it from the picture can spell significant improvements in heart health.35 A high body-fat percentage is another such risk factor, so if MOTS-c can prevent obesity, it can halt the onset of a health condition characteristic of more than 80% of people with coronary heart disease.36 37
• Longevity: Given the link between inflammation, age, and high-risk age-related diseases (e.g., atherosclerosis, cardiovascular disease), MOTS-c may increase lifespan as a continual downstream effect.38
• Cognitive function: A 2022 review published in Progress in Neurobiology noted that “metabolic modulators” (which MOTS-c is) and exercise (which MOTS-c simulates) can be used in neuroprotective strategies.39 Or at least that has been the case in preclinical studies.

Keep in mind that these downstream effects are based on deduction, so they’re largely hypothetical. We need more studies examining MOTS-c’s direct effects on human health before we can conclusively say it offers such therapeutic benefits.

MOTS-c’s safety profile is currently incomplete, as human trials and controlled use cases are lacking. But we can say that scientific opinion seems to lean more toward “safe” than “unsafe.”

For example, in a 2021 Cognitive Vitality Report, the Alzheimer’s Drug Discovery Foundation points to a short-term study on CB4211 as some evidence for MOTS-c’s safety.40 CB4211 is an analog, or synthetic version, of MOTS-c, and so it should theoretically pose a similar set of risks.41 The study in question was a double-blind, placebo-controlled trial in adult humans using single and multiple ascending doses, under which protocol CB4211 was found to be “safe and well tolerated.”42

Even if MOTS-c is as safe as CB4211, clinical researchers and the healthcare providers we know warn that it potentially poses specific health risks.

The most alarming of these is its cancer risk. Despite the research saying that MOTS-c may be useful as a cancer therapy, other studies have made a contradicting claim that it can lead to the development of prostate and breast cancer.43 Our known providers likewise warn that people with an active cancer diagnosis should avoid MOTS-c unless otherwise recommended by their doctor.

In addition, the Cognitive Vitality Report mentions some potential drug interactions, namely any medications that activate AMPK. That includes antidiabetic drugs like metformin, insulin-sensitizing drugs like thiazolidinediones, and over-the-counter drugs like aspirin.44 Meanwhile, the U.S. Anti-Doping Agency (USADA) states there are numerous reported side effects of MOTS-c among people who purchase it online, such as:45

• Injection site irritation
• Heart palpitations
• Insomnia
• Fever

Our known providers add that MOTS-c may also cause headache, flushing, fatigue, and mild gastrointestinal symptoms such as nausea and stomach discomfort.

Research-grade vs. pharmaceutical-grade MOTS-c

MOTS-C can be found in pharmaceutical-grade form, but much of it is currently research-grade material. That means it’s largely relegated to laboratory use and is not suitable for human consumption.

Being a research-grade peptide allows it to be sold without a prescription, so you can easily purchase it online, but we don’t recommend that you do so. Research-grade peptides often lack the quality controls that go into pharmaceutical-grade products, resulting in a drug whose purity reaches as low as 60%.46 The potentially high proportion of impurities can be toxic — possibly accounting for those “numerous reported side effects” per the USADA — and poses a risk of immunogenicity, a condition in which the body interprets an exogenous substance as a threat and mounts an immune response against it.46 Said immune response can be life-threatening.47

But like we said, you can find pharmaceutical-grade MOTS-C; it’s just not as common as its research-grade counterpart. If you’re interested in MOTS-C treatment, speak with your doctor to discuss getting a prescription from an accredited pharmacy.

Our known healthcare providers have shared their knowledge of how a standard MOTS-c treatment protocol would proceed. We break down this protocol in the following sections.

Dosing and administration

A dose of MOTS-c ought to start around 5mg per injection. As with many therapeutic peptides, you can expect it to come as a month’s supply of reconstitutable powder, along with bacteriostatic water and needle syringes. To reconstitute the powder, you should follow your provider’s instructions on dissolving it in the bacteriostatic water. Normally, you should avoid shaking the mixture, which can degrade the peptide.

Treatment protocol

MOTS-c is a twice-weekly treatment, which seems more easily manageable than the near-daily injections you’d undergo with other peptides, like CJC-1295. The time of day doesn’t matter necessarily, but a morning injection would allow you to take advantage of MOTS-c’s potentially energizing effects (and avoid an energy boost when you’re heading to bed).

Injections are subcutaneous into a fatty area such as a thigh, an upper arm, or the belly. Our providers recommend rotating your injection sites to minimize the risk of injection site reactions.

You may begin to feel the benefits of your treatment in as little as 1-2 weeks, as your improved metabolism and mitochondrial function lead to higher energy levels. Weeks 4-6 are when you might notice improvements in physical performance, such as increased stamina and endurance. Meanwhile, reduced inflammation may allow you to experience a general boost in your physical and mental well-being.

Storage

After reconstitution, therapeutic peptides are best kept under refrigeration — around 4°C, or 39°F.48 Peptides should keep for a month under these conditions. There’s usually no need to transfer the peptide to an air-safe container since the vial will probably be sealed with a self-healing stopper (a rubber top that seals around any punctures made with a needle).

The potential benefits on mitochondrial health that MOTS-C has shown in research suggest it may be suitable for those who have or are at risk for:

• Diabetes
• Obesity
• Chronic inflammation
• Osteoporosis
• Age-related declines (e.g., sarcopenia)

Its energizing action on skeletal muscle also makes it an enticing treatment for amateur athletes and strength trainers, with increased exercise capacity leading to better performance or faster gains.

However, MOTS-c should be avoided by professional athletes on the competitive circuit. The World Anti-Doping Agency includes MOTS-c under Section 4 of its Prohibited List, so at no time is it permissible for use by athletes participating in official competition.49 If you do use it, you may be disqualified after your next drug test.

MOTS-c is also contraindicated for people who take AMPK-activating medicines, such as metformin, thiazolidinediones, and aspirin, as well as anyone with an active cancer diagnosis and people who are pregnant or breastfeeding.

Pharmaceutical-grade MOTS-c is relatively scarce at this time, but it’s out there. To get some, you’ll need a prescription from a doctor and have to purchase it from an accredited pharmacy. If you work through an online platform, make sure that they are offering pharmaceutical or medical-grade peptides.

You can easily find research-grade product online, but that isn’t a route we recommend you take, considering the dangers involved. Remember, research-grade peptides aren’t intended for human consumption and may contain a high percentage of impurities that can lead to potentially life-threatening circumstances, such as immunogenicity.46 47

We’ll be watching MOTS-c closely as it progresses through the research space. As more human trials enter the literature and availability broadens, we’ll update this guide accordingly and eventually point you to reliable channels through which to obtain the promising peptide.