Mitochondrial ORF of the 12S rRNA type-c · MOTSc · MOTS c
Highest evidence
Human trial
Studies recorded
4· 1 in humans
Legal status · US
Unapproved
Scientific context only. Not medical advice, not a recommendation to use.
At a glance
MOTS-c is a 16-amino-acid mitochondrial-encoded peptide (mitochondrial-derived peptide, MDP) whose open reading frame lies within the 12S rRNA region of mitochondrial DNA. In basic research (including the laboratories of Changhan Lee and Pinchas Cohen) it is described as a regulator of metabolic homeostasis and an activator of the AMPK pathway, and is sometimes discussed as an 'exercise mimetic'. The evidence comes almost entirely from cell and animal models; controlled human trials of MOTS-c as a therapeutic are lacking. It is not approved as a medicine anywhere and is traded on the grey market as a research chemical.
Researched for
Metabolic homeostasis and insulin sensitivity (preclinical)Age-related physical decline (animal model)Obesity and diet-induced insulin resistance (animal model)
Official status
US: Unapproved
No FDA approval; not an approved medicine and not a dietary supplement. MOTS-c is on the WADA Prohibited List (section S4.4, metabolic modulators / AMPK activators) and is banned in sport at all times. It is sold predominantly as a 'research chemical' without legal cover for human use.
MOTS-c arises from a short open reading frame located in the 12S rRNA region of the mitochondrial genome — unlike most peptides it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes MOTS-c as modulating the folate cycle and the de novo purine biosynthesis tethered to it, thereby affecting the AMP/ATP ratio and, downstream, AMP-activated protein kinase (AMPK). Under metabolic stress, an AMPK-dependent translocation of the peptide into the cell nucleus and involvement in the regulation of stress-responsive genes (including via antioxidant-response-element-regulated transcription factors) have also been reported. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic MOTS-c is not established by human studies.
02
Evidence at a glance
Reading note. The distribution shows on which evidence tier each observation sits. Strong colours mark stronger evidence — weaker tiers are deliberately visible, not hidden.
4 observations · 2 tiers
Human trial
1
Animal model
3
03
What the studies show
Animal model
Maus / Zellkultur
Lee C, Zeng J, Drew BG, et al. 2015
Activation of the AMPK pathway and improved glucose handling in cell and mouse models
What does NOT follow: Finding from preclinical models. Whether these metabolic effects reproduce in humans after administration of synthetic MOTS-c is not established by controlled human trials.
Animal model
Maus
Lee C, Zeng J, Drew BG, et al. 2015
Prevention of diet- and age-induced insulin resistance and diet-induced obesity in treated mice
What does NOT follow: Pure animal-model result. No inference about treating obesity or diabetes in humans can be drawn from it.
Animal model
Maus
Reynolds JC, Lai RW, Woodhead JST, et al. 2021
Improved physical performance and running capacity in young, middle-aged and old mice under intermittent MOTS-c administration
What does NOT follow: Animal-experimental observation. The popular term 'exercise mimetic' is a hypothesis from preclinical data and not a proven clinical effect in humans.
Human trial
Mensch (Beobachtung)
Reynolds JC, Lai RW, Woodhead JST, et al. 2021
Endogenous blood and skeletal-muscle MOTS-c levels change in humans in association with physical activity
What does NOT follow: This concerns endogenous levels as a correlate of exercise — it is not a statement about the efficacy or safety of exogenously administered synthetic MOTS-c. Observational data do not permit causal inference.
04
Where studies disagree
Open question
Does exogenously administered MOTS-c improve metabolism or performance in humans?
POSITION A
Preclinical studies show consistent AMPK-mediated metabolic and performance effects in cells and mice.
POSITION B
There are no controlled human trials of administered synthetic MOTS-c; human data are limited to observations of endogenous levels in association with exercise.
CURRENT STATE · The evidence is mechanistically and preclinically interesting but insufficient for any human assessment. Statements about therapeutic benefit or safety in humans are currently not supported by clinical evidence.
05
Pharmacokinetics
No robust pharmacokinetic human data available. A model curve is not invented.
06
Routes of administration in the literature
Which routes of administration the available studies describe — neutral reporting, not a usage guide.
Other
In preclinical studies MOTS-c was administered to rodents predominantly by injection (including intraperitoneally). This describes study practice in the animal model and is not a statement about human use.
06d
Safer use & risks
Risk notes for harm reduction — descriptive, not a usage or dosing guide.
⚠ Important — please read
This platform does NOT provide usage or dosing instructions. The points below describe risks and are meant to help avoid harm — they do not replace medical advice. Anyone who uses a substance should discuss it with a doctor.
There is no approved human use for this substance. What circulates online about amounts and frequency is self-experimentation without a safety net.
Online numbers are not a benchmark
Amounts from TikTok, YouTube and forums are mostly imitation rather than data — and are often wrongly derived from animal studies (µg/kg). Not a reliable benchmark for humans.
Sterility & infection risk
Injection solutions prepared or stored non-sterile carry an infection and abscess risk. Contamination is common with grey-market product.
Unknown product quality
Research-/grey-market product is not quality-tested: identity, purity and actual content are often unknown, and counterfeits occur.
Mind interactions
Combinations with medications or pre-existing conditions can carry risks (see the Interactions section). Clarify with a doctor beforehand.
Warning signs — seek medical help
With persistent pain, redness/swelling at the injection site, fever, shortness of breath, racing heart, chest pain or allergic reactions, seek medical help immediately.
A doctor, not a forum
Concrete questions about use and amount belong in a conversation with a doctor — not in a comment thread.
07
Known adverse events from studies
Factual reporting of what studies observed. Not a safety statement for individual use.
Theoretical
No systematically collected human safety profile for synthetic MOTS-c available
There are no published controlled human trials on adverse events under exogenous MOTS-c. The absence of documented side effects is not evidence of safety but a reflection of missing data.
keine belastbaren Daten
07b
Interactions & combinations
Documented interactions and contraindications from studies, prescribing information and guidelines. Where no data exists, this is stated.
Reporting of risks, NOT a combination guide. The absence of an entry does not mean „safe to combine“ but „not sufficiently studied“.
No documented interactions recorded
We have not yet found robustly documented interactions for this peptide. This does NOT mean none exist — the data is limited.
08
Risks & hygiene aspects in the literature
What regulatory and scientific literature reports on risks, sterility and identity in non-pharmaceutical sources — descriptive, not a hygiene guide.
'Exercise mimetic' as a hypothesis, not a proven human effect
The term 'exercise mimetic', popular in media and marketing, derives from animal and mechanistic studies. Controlled human trials demonstrating that exogenous MOTS-c improves physical performance or metabolism in humans are lacking.
10
Anecdotal observations
Weakest evidence tier — not supported by studies
Reading note. This section gathers popular claims from communities and forums. They are explicitly marked as weakest-tier evidence. Unblinded self-reports are particularly prone to placebo, recall and confirmation biases.
Why no amounts or protocols are listed here. We deliberately show only WHAT communities report — not in what amount or how it is used. Anecdotal "doses" or "biohacker protocols" are neither verified nor standardised nor safe; publishing them would be a usage guide, which we do not provide on principle. Specific amounts belong in a conversation with a doctor, not in a forum.
In anti-aging and fitness circles MOTS-c is marketed as 'exercise in a syringe' or as an agent against age-related decline.
common in English-language longevity and biohacking communities
Not supported by studies: These claims rest on animal models and observations of endogenous levels, not on controlled human trials with exogenous MOTS-c. Purity and identity of grey-market products are not assured.
11
Legal status by country
Country
Status
Note
Checked
United States
Unapproved
No FDA approval; not an approved medicine and not a dietary supplement. MOTS-c is on the WADA Prohibited List (section S4.4, metabolic modulators / AMPK activators) and is banned in sport at all times. It is sold predominantly as a 'research chemical' without legal cover for human use.
2026-06-07
Germany
Unapproved
No EMA or national approval as a medicine. Placing it on the market for human use is not legally covered; sale as a research chemical does not circumvent medicines-law requirements. In organised sport the WADA ban (S4.4) applies.
2026-06-07
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Reconstitution calculator
Pure mg/mL maths — works like a calculator. Not a usage recommendation.
Peptides ship as a dry powder. Once dissolved in a liquid (reconstitution), this calculator answers a single question: how much substance is in one millilitre of solution afterwards?
1Enter the vial's substance amount (printed on the label).
2Enter how much solvent you add.
3Result = concentration in mg per mL.
Printed on the label
/
Liquid you add
=
2.50
mg / mL
5 mg in 2 mL gives 2.50 mg/mL — each millilitre contains 2.50 mg of substance.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Findings:MOTS-c is induced by exercise; in animal models it improved physical capacity and countered age-related muscle decline. In humans it rises in muscle/blood after exertion.
Limitations:Efficacy evidence predominantly animal; human data so far observational (expression), not interventional.