MOTS-c
/mots-SEE/aka Mitochondrial open reading frame of the 12S rRNA-c, MOTSc, Mitochondrial-derived peptide
A 16-amino-acid peptide encoded in mitochondrial DNA that activates AMPK and acts like an exercise signal in mice.
MOTS-c: educational research discussion. Not medical advice. Not a protocol for you.Details
- Reported range
- 5–10 mg per week
- Frequency
- 2–3× weekly
- Cycle length
- Not standardized
- Half-life
- Unknown in humans
- Route
- SC
Reported figures describe what is published or discussed. None of them is a dose for you.
Mechanism
What it is proposed to do
MOTS-c is encoded by a short open reading frame inside the mitochondrial 12S rRNA gene. In cell and mouse studies it acts mainly on skeletal muscle. It inhibits the folate cycle, which raises levels of AICAR, an AMPK activator. Under metabolic stress it moves into the nucleus and changes gene expression. Endogenous MOTS-c rises with exercise in humans. Whether injected MOTS-c does anything in people is untested.
- 01
MOTS-c
16-aa peptide from the mitochondrial 12S rRNA gene
established - 02
Folate cycle ↓ · AICAR ↑
Shown in cells and mice (Lee 2015)
proposed - 03
AMPK activation · nuclear gene regulation
Moves into the nucleus under metabolic stress in cell studies (2018)
proposed - 04
Insulin sensitivity ↑ · exercise capacity ↑
Diet-induced obesity and ageing models in mice
proposed
Half-life. Unknown in humans. We found no published human pharmacokinetic data for MOTS-c itself.
Dosing & cycles
What is reported, and where it comes from
Numbers below are labeled FDA label, clinical trial range or commonly reported range. They describe the published and discussed landscape. They are not instructions and not a protocol for you.
Dosing studio
Every figure is labeled by where it comes from.
Scale view: Commonly reported weekly total
Probe at 7.5 mg: inside the reported band (5–10 mg). Drag it to read the scale. It does not pick a number for you.
Typical cycle, as a calendar
Community pattern: 2–3× weekly
Not standardized
Injections spread across the week, echoing the 3×/week schedule used in old mice (Reynolds 2021). The 8-week block shown is illustrative. No human data define a length or a break.
Cycle patterns
Community pattern: 2–3× weekly
Injections spread across the week, echoing the 3×/week schedule used in old mice (Reynolds 2021). The 8-week block shown is illustrative. No human data define a length or a break.
Stacks
What it gets combined with
Why people pair things, and what nobody has tested.
Mito stack
3 compounds- Why people combine these
- Grouped under "mitochondrial support": an AMPK-linked peptide plus compounds pitched to raise NAD+.
- Caution
- Three compounds, zero combined human data. 5-amino-1MQ has no human data even on its own.
- What is unknown
- No published human data on this combination: dosing, interactions and long-term effects are all unstudied.
MOTS-c + GLP
3 compounds- Why people combine these
- Pitched as protecting muscle and metabolic fitness during GLP-1 weight loss.
- Caution
- The GLP-1 half has the evidence. The MOTS-c half is mouse data, and no study has tested the pair.
- What is unknown
- No published human data on this combination: dosing, interactions and long-term effects are all unstudied.
Evidence
How much of this is known
Evidence grade
C
Thin human data
Human data thin (pilots, uncontrolled, or none completed). Strong animal data and a lot of anecdote.
How we gradeGraded C rather than D because the mouse data are consistent across several labs and an analog reached a small Phase 1b. No completed human trial of MOTS-c itself.
Human trial status
No completed human trial of MOTS-c itself. Human data are observational: circulating MOTS-c rises with exercise, and levels track with metabolic traits in small cohorts. CohBar's analog CB4211 finished a Phase 1a/1b in 2021. In 20 adults with obesity and fatty liver, 4 weeks of daily injections lowered ALT, AST and glucose versus placebo, but liver fat fell about equally in both groups. CohBar later said that formulation was not suitable for further development. A 120-person Phase 2a of MOTS-c in prediabetes was registered in 2026 and has not reported.
Limitations
- CB4211 is a modified analog, so its results do not transfer directly to MOTS-c.
- The CB4211 Phase 1b was small (20 people), short (4 weeks) and company-reported.
- Doses discussed online are extrapolated from mouse studies.
- No human pharmacokinetic data for MOTS-c itself.
Sources to read
- Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Cell Metab 2015)
- Kim KH et al. MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress (Cell Metab 2018)
- Reynolds JC et al. MOTS-c is an exercise-induced regulator of age-dependent physical decline and muscle homeostasis (Nat Commun 2021)
- CohBar. Phase 1a/1b study of CB4211, a MOTS-c analog (NCT03998514; topline results August 2021)
- Phase 2a trial of MOTS-c in prediabetes and overweight/obesity (NCT07505745; registered 2026, recruiting)
- FDA Pharmacy Compounding Advisory Committee, July 23–24, 2026
Links open PubMed, DailyMed, FDA or trial-registry searches. We do not cite what we have not described accurately.
Safety
Side effects, cautions, status
Commonly reported effects
- Human safety data exist only for the analog CB4211. In its Phase 1a/1b the company reported no serious adverse events; injection-site reactions were the only events above 10%.
- No published human safety data for MOTS-c itself.
- It improves glucose handling in mouse models. Effects on blood sugar in people, including those on diabetes drugs, are unknown.
- Product quality is the largest practical risk: gray-market vials vary in purity, content and endotoxin.
Who should be extra cautious
- Tested athletes. Prohibited at all times (WADA S4.4.1, named).
- Diabetes or glucose-lowering drugs. Glucose effects seen in mice. No human data on the combination.
- Pregnancy or breastfeeding. No data at all.
- Gray-market product. Purity, dose accuracy and endotoxin vary between vendors and batches.
Legal & regulatory status
Not approved as a drug anywhere. In April 2026 FDA removed it from its Category 2 compounding-risk list. In July 2026 an FDA advisory committee voted to recommend it for the 503A bulks list. Until FDA finishes rulemaking, compounding it is not authorized.
2026 compounding context. April 15, 2026: removed from Category 2. July 23–24, 2026: FDA's Pharmacy Compounding Advisory Committee recommended MOTS-c for the 503A bulks list. The vote is advisory. Legal compounding requires notice-and-comment rulemaking and a final FDA rule.
WADA. Prohibited at all times. Named under S4.4.1 (metabolic modulators, AMPK activators) alongside AICAR.
Storage & handling, high level
Sold as lyophilized powder. Reconstituted peptides are generally kept refrigerated, away from light, and degrade over weeks. We found no stability data specific to MOTS-c, so any shelf-life claim is a guess.
Reconstitution and injection technique are clinical skills. The reconstitution calculator does arithmetic only.
FAQ
Questions people ask about MOTS-c
Is MOTS-c an exercise pill?
Wasn't it tested in humans?
Is it legal to compound now?
Is it banned in sport?
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