Updated August 2026
MOTS-c Peptide: Dosage, Human Trials, Results, Side Effects & FDA Status
Research status: MOTS-c is an investigational mitochondria-derived peptide. It is not FDA approved for any indication, has no established human dosage, and has no published results from a completed trial in which native MOTS-c was administered to people. A 120-participant Phase 2a trial is recruiting, but its fixed dose is not publicly disclosed. The completed human study frequently described as a “MOTS-c trial” tested CB4211, a modified MOTS-c analog, not native MOTS-c.
MOTS-c—short for mitochondrial open reading frame of the 12S rRNA type-c—is a 16-amino-acid signaling peptide encoded within mitochondrial DNA. Laboratory and animal studies connect it to cellular energy sensing, AMPK signaling, glucose handling, skeletal-muscle metabolism, exercise capacity, and stress-responsive gene expression. Those findings are biologically interesting, but most claimed benefits remain unproven in people.
The first registered randomized study administering native MOTS-c for a metabolic indication, MOTS-MET (NCT07505745), began in 2026. It plans to randomize 120 adults with prediabetes and overweight or obesity to once-daily subcutaneous MOTS-c or placebo for 12 weeks. No results have been posted, and the public registry does not disclose the dose.
MOTS-c is often marketed for weight loss, endurance, muscle preservation, recovery, insulin resistance, and longevity. As of this update, none of those uses is supported by a completed controlled human trial of native MOTS-c.
This page is an evidence reference, not a dosing recommendation or medical advice. It does not include a reconstitution calculator, titration chart, or human dose converter.
30-Second Summary
| Question | Answer |
|---|---|
| What is it? | A naturally occurring 16-amino-acid mitochondrial-derived peptide encoded within MT-RNR1/12S rRNA |
| Main proposed mechanism | Metabolic-stress signaling involving the folate–purine–AICAR–AMPK axis, nuclear translocation, and context-dependent nuclear gene regulation |
| Studied administration | Native MOTS-c: once-daily SC in an ongoing Phase 2a trial (dose undisclosed); most published intervention evidence is rodent IP |
| Established human dosage | None |
| Strongest human evidence | Recruiting Phase 2a; exercise-related endogenous MOTS-c changes; observational biomarker and genetic studies |
| Strongest administered result | Improved metabolic and physical-performance outcomes in mouse models — not demonstrated in humans |
| Known side effects | No established adverse-event profile for native MOTS-c in humans |
| FDA status | Not approved; not a component of an FDA-approved drug |
| Compounding status | July 2026 PCAC recommended possible 503A inclusion 7–5 (2 abstentions) — nonbinding |
| Sport status | Prohibited at all times by WADA as an AMPK activator |
What Is MOTS-c?
MOTS-c is a small protein—often called a peptide or microprotein—made from a short open reading frame embedded in the mitochondrial 12S ribosomal RNA region. Reported human sequence: MRWQEMGYIFYPRKLR (~2,174.6 g/mol free base). Discovered in 2015 by Lee and colleagues.
Calling MOTS-c a “mitochondrial peptide” does not mean an injected product simply supplies energy to mitochondria. Research describes MOTS-c as a signaling molecule that can alter cellular metabolism and, under stress, move into the nucleus and influence gene expression. No definitive cell-surface receptor has been established.
| Property | Verified description |
|---|---|
| Full name | Mitochondrial open reading frame of the 12S rRNA type-c |
| Length | 16 amino acids |
| Genetic origin | Short ORF within mitochondrial 12S rRNA/MT-RNR1 |
| Endogenous presence | Detected in human and rodent tissues and circulation |
| Main research tissues | Skeletal muscle, metabolic tissues, bone, cardiovascular tissue |
| Known receptor | No definitive cell-surface receptor established |
| Regulatory status | Investigational; not an approved medicine |
MOTS-c Evidence Map: Four Different Questions
Many MOTS-c pages mix unlike forms of evidence. The distinctions below are essential. The strongest conclusion supported today is that MOTS-c is a biologically active mitochondrial signal with substantial preclinical research and an emerging human-development program — not a clinically validated metabolic, performance, muscle-building, or longevity therapy.
MOTS-c evidence ladder
Preclinical depth ≠ clinical proof
- 1
Molecular mechanism
CellFolate/purine signaling, AICAR, AMPK, nuclear translocation, CK2 binding
- 2
Cell studies
CellGlucose metabolism, myostatin signaling, stress responses, 2026 stromal-cell repair paradox
- 3
Animal studies
AnimalWeight-gain prevention, glucose disposal, treadmill capacity, muscle atrophy, bone/CV models
- 4
Endogenous human studies
Measured in humansExercise response, biomarker associations, muscle correlations
- 5
Human genetic studies
Association onlym.1382A>C/K14Q; n=27,527; sex/activity interaction
- 6
Native-MOTS-c intervention
PendingMOTS-MET recruiting; no results
- 7
Approval
PendingNone — not FDA approved
| Evidence lane | What was studied? | What it can answer | What it cannot answer |
|---|---|---|---|
| Endogenous human physiology | MOTS-c already present in blood or tissue | Whether levels change with exercise, age, obesity, diabetes | Whether an injected product works or is safe |
| Human genetic studies | Natural mtDNA variants that alter MOTS-c | Whether MOTS-c biology may be relevant to metabolic traits | The effect of administering synthetic MOTS-c |
| Cell and animal intervention | Synthetic MOTS-c in cells or rodents | Mechanism, plausibility, animal-model effects | Human dose, efficacy, safety, or clinical outcomes |
| Human drug trials | Native MOTS-c or a defined analog given to people | Product-specific safety and efficacy | Results for a different molecule, formulation, or population |
MOTS-c Dosage: No Established Human Dose
There is no FDA-approved or clinically established MOTS-c dosage. No completed peer-reviewed trial has defined a safe, effective dose of native MOTS-c in humans.
Five- and ten-milligram protocols are widely repeated online. In FDA’s 2026 review, 5 mg and 10 mg were the proposed vial strengths in a withdrawn compounding nomination — not evidence-based clinical dosages. The nomination did not adequately specify reconstitution volume, concentration, formulation, or free base versus acetate.
Animal milligram-per-kilogram amounts cannot be converted into a defensible human dose. FDA found no in-vivo pharmacokinetic or toxicokinetic study of MOTS-c.
- No validated dose-escalation schedule exists. MOTS-MET uses a fixed once-daily dose (undisclosed); no titration is listed.
- This page does not publish a titration chart, reconstitution calculator, “units” calculator, or week-by-week protocol.
Research exposures — not dosing recommendations
| Compound | Population/model | Dose | Route / duration | Role |
|---|---|---|---|---|
| Native MOTS-c | Prediabetes + BMI 27–40 (MOTS-MET) | Not publicly disclosed | Once-daily SC × 12 weeks | Recruiting Phase 2a |
| Compounded nomination | FDA nomination — not a clinical study | 5 mg and 10 mg vial strengths proposed | Proposed SC; not established | Not evidence-based doses |
| CB4211 analog | Obesity + NAFLD | 25 mg once daily | SC × 4 weeks | Completed Phase 1b — different molecule |
| Native MOTS-c | HFD mouse model | 0.5 mg/kg/day | IP × 8 weeks | Preclinical metabolism |
| Native MOTS-c | Mouse insulin-sensitivity experiments | 5 mg/kg/day | IP up to 7 days | Preclinical glucose disposal |
| Native MOTS-c | Mouse exercise studies | 5 or 15 mg/kg | IP; acute to long-term | Preclinical treadmill capacity |
MOTS-MET Phase 2a Trial: The First Direct Human Efficacy Test
The most important current development is MOTS-MET (NCT07505745), a registered Phase 2a trial of native MOTS-c. A registered trial is a research plan, not a positive result.
MOTS-MET trial tracker
First randomized native-MOTS-c metabolic efficacy test
Registration is not a result. No outcomes posted; dose remains undisclosed.
- NCT
- NCT07505745
- Status
- Recruiting
- Planned n
- 120
- Population
- Adults 18–65; BMI 27–40; prediabetes
- Regimen
- Fixed once-daily SC dose — amount not publicly disclosed
- Treatment / safety
- 12 weeks · safety Through Week 16
- Primary efficacy
- Change in OGTT Matsuda Index at Week 12
- Primary safety
- Treatment-emergent adverse events
- Study start
- February 2, 2026
- Est. primary completion
- February 2027 (estimate; may change)
- Results posted
- No
- Site note
- Peking University Shenzhen Hospital (registry site)
MOTS-c Results: What Has Actually Been Measured?
Administered native MOTS-c has not been shown to improve insulin sensitivity, cause weight loss, or improve endurance in people. Endogenous levels change with exercise; circulating levels show mixed diabetes/obesity associations; mouse models show metabolic and treadmill effects.
Claim vs evidence checker
Marketing claim → best evidence → verdict
Weight loss
High-fat-diet mouse models (~20% lower final weight vs vehicle HFD)
Not demonstrated in humans
Better insulin sensitivity
Mice; MOTS-MET human trial pending
Not demonstrated after human dosing
More endurance
Mouse treadmill studies (young, middle-aged, old)
Not demonstrated in humans
Muscle growth
Cell/mouse anti-atrophy / myostatin signaling
No human hypertrophy evidence
Faster recovery
No controlled human study; 2026 stromal-cell result raises context concern
Unsupported
Longer life
Mouse healthspan; numerical lifespan ↑ but overall curve P=0.23
No human evidence
Exercise replacement
Mechanistic overlap + endogenous exercise response
Misleading
Human evidence type toggle
Keep administered, endogenous, genetic, and analog lanes separate
MOTS-MET Phase 2a
Planned n=120; prediabetes + BMI 27–40
Exposure: Fixed once-daily SC dose — amount undisclosed
No results posted
Registration is not a result
View source →
Human MOTS-c Research
Human studies that measure the MOTS-c naturally produced by the body do not demonstrate that injected MOTS-c is effective or safe.
Exercise changes endogenous MOTS-c
Reynolds et al. (2021): in 10 young men after cycling, skeletal-muscle MOTS-c increased (P=0.0098) and circulating MOTS-c changed at post-exercise time points. This supports exercise responsiveness — not that injecting MOTS-c reproduces exercise.
Circulating MOTS-c and metabolic disease
A 2024 meta-analysis (7 studies, n=602) found lower circulating MOTS-c in diabetes (SMD −0.89) but higher levels in an obesity subgroup after excluding overweight-only groups (SMD +0.51). These inconsistent patterns argue against a simple deficiency narrative.
K14Q mitochondrial-DNA variant
m.1382A>C (rs111033358) creates K14Q MOTS-c. Across 27,527 participants, the C allele associated with higher type 2 diabetes prevalence in men (esp. low activity). Wild-type MOTS-c improved mouse metabolic outcomes where K14Q did not — biological relevance, not treatment proof.
Human biomarker results explorer
Every entry states blood, tissue, genotype — or administered intervention
Reynolds 2021 exercise
Tissue + bloodNot administeredn=10 young men
Muscle and serum MOTS-c rose after cycling
Zhou 2024 meta-analysis
BloodNot administeredn=602
↓ in diabetes; ↑ in obesity subgroup; + correlations with TC/LDL
Kumagai 2021
BloodNot administeredn=Japanese men cohort
Inverse correlation with plasma myostatin
Zempo 2021 genetics
GenotypeNot administeredn=27,527
K14Q associated with higher T2D in men (esp. low activity)
MOTS-c Results in Animal and Cell Research
Preclinical studies support a metabolic research hypothesis. They do not provide a “before and after” expectation for people, and their doses should not be converted into self-administration protocols.
A June 2026 stromal-cell study found MOTS-c activated AMPK in cells from donors with obesity and reduced proliferation, increased p16/p21 and TNF-α, and failed to restore reparative function — showing why “AMPK activation” cannot automatically mean anti-aging or recovery.
Animal study explorer
Animal doses visible for fidelity — human conversion disabled
- Metabolism
Male mice, 60% HFD
0.5 mg/kg/day IP × 8 weeks
~20% lower final body weight; ↑ energy expenditure; less liver fat
Prevention of mouse weight gain ≠ human weight-loss evidence
- Metabolism
Adult male mice, glucose clamp
5 mg/kg/day IP
~30% higher glucose-infusion requirement during insulin stimulation
Short animal physiology experiment
- Metabolism
Older insulin-resistant mice
5 mg/kg/day IP × 7 days
Restored ex-vivo soleus insulin responsiveness toward young levels
Tissue-specific animal result
- Metabolism
Obese male mice
2.5 mg/kg IP twice daily × 3 days
~50% lower blood glucose + metabolite changes
Very short study; not a clinical endpoint
- Exercise
Young / middle-aged / old mice
5 or 15 mg/kg IP (acute to multi-week)
Improved treadmill performance; stronger effects at 15 mg/kg in young mice
Cannot be assumed in human athletes
- Muscle
HFD mouse + cell myotubes
0.5 mg/kg/day × 3 weeks (mouse arm)
Reduced myostatin signaling; protection vs HFD relative muscle-mass loss
Preclinical anti-atrophy — not human hypertrophy
- Aging
Late-life male mice from 23.5 months
15 mg/kg 3×/week
Median 970 vs 912 days; max 1,120 vs 1,047; overall curve P=0.23
Healthspan clearer than definitive lifespan extension
- Bone
Ovariectomized mice
5 mg/kg/day IP × 12 weeks
Less weight/fat gain; improved glucose tolerance; bone/metabolic markers
Menopause-related mouse model
- Cardiovascular
Rodent vascular / myocardial models
Experiment-specific
Vascular calcification, remodeling, high-altitude cardiac studies reported
Preclinical only — no human CV outcomes
- Pancreas
Islet senescence models
Experiment-specific
Reported effects on islet senescence and glucose tolerance
Not an established diabetes treatment
MOTS-c Side Effects
The side effects of native MOTS-c in humans are not established. No published completed interventional trial provides adverse-event rates for the native peptide. Lists that confidently name nausea, fatigue, flushing, or injection-site percentages as established MOTS-c side effects are not grounded in published native-MOTS-c trial data.
Safety unknowns matrix
No native-MOTS-c AE percentage chart until trial-arm data exist
| Domain | Status | Note |
|---|---|---|
| Human pharmacokinetics | Not studied | FDA found no in-vivo PK/TK |
| Human half-life | Not studied | In-vitro blood cleavage ≠ clinical half-life |
| Dose-response | Not studied | No published human dose-response |
| Common adverse events | Not studied | No completed native-MOTS-c AE table |
| Serious adverse events | Not studied | No controlled human dataset |
| Immunogenicity | Pending | MOTS-MET plans anti-drug antibody assessment |
| Drug interactions | Not studied | Including glucose-lowering drugs |
| Reproductive toxicity | Not studied | FDA: no DART package identified |
| Genotoxicity | Not studied | FDA: no studies identified |
| Carcinogenicity | Not studied | FDA: no studies identified |
| Organ-lab effects | Not studied | No native-MOTS-c safety tables |
| Long-term safety | Not studied | Unknown |
FDA’s 2026 safety assessment
- No human exposure data through any route at the time of review
- No clinical PK, acute toxicity, repeat-dose toxicity, genotoxicity, DART, or carcinogenicity studies identified
- Concerns about peptide aggregation, impurities, immunogenicity, free base vs acetate ambiguity, and injectable-product quality
- FAERS search through March 9, 2025 retrieved no reports — that does not establish safety
What the CB4211 Analog Trial Does—and Does Not—Tell Us
CB4211 is a drug candidate derived from MOTS-c biology, but it is a modified analog. Its trial cannot be used to assign a dose, benefit, side effect, or half-life to native MOTS-c.
MOTS-c vs CB4211 identity card
Prevents the most common evidence-transfer error
| Field | Native MOTS-c | CB4211 analog |
|---|---|---|
| Molecule | Native 16-aa MOTS-c (MRWQEMGYIFYPRKLR) | Modified MOTS-c analog |
| Clinical phase | Phase 2a recruiting (MOTS-MET) | Completed Phase 1a/1b |
| Population | Prediabetes + overweight/obesity (planned) | Healthy adults; obesity + NAFLD |
| Dose disclosed? | No — fixed daily SC, amount undisclosed | Yes — 25 mg SC daily in Phase 1b |
| Results | None posted | Sponsor: ↓ ALT/AST/glucose; liver fat ≈ placebo |
| Adverse events | Unknown for native peptide | Injection-site reactions >10%; no SAEs reported in Phase 1b |
| Development status | Active recruiting trial | Original developer moved toward dissolution; no active pivotal program identified |
How MOTS-c Works
MOTS-c appears to act as a message from mitochondria to the rest of the cell. When energy or nutrient conditions change, it can influence pathways that help cells adjust fuel use and stress responses — including AMPK activation and nuclear translocation. This is not equivalent to “making more ATP,” and it does not prove clinical benefits in people.
Unlike GLP-1 drugs, MOTS-c does not have a fully characterized clinical receptor–dose–response framework. CK2 has been identified as a direct binding partner in skeletal-muscle research, but FDA’s 2026 review still described overall molecular targets as unresolved.
Metabolic mechanism visualization
Two linked routes — clinical benefits remain hypothesized
Metabolic route
MOTS-c → one-carbon/purine metabolism → AICAR accumulation → AMPK → glucose and lipid handling
- GLUT4 translocation (cells/animals)
- PGC-1α / AMPK (2026 ex-vivo)
Definitive upstream receptor: unresolved. Downstream clinical benefits are hypothesized or preclinical — not proven in humans.
MOTS-c vs Similar Compounds and Interventions
No head-to-head human trial has compared MOTS-c with the compounds below. The table compares mechanisms and evidence maturity — not efficacy.
| Compound/intervention | Main mechanism | Human evidence | Key distinction |
|---|---|---|---|
| MOTS-c | Mitochondrial stress signaling; AMPK-linked adaptation | Endogenous physiology; recruiting Phase 2a | Native 16-aa mitochondria-encoded peptide |
| CB4211 | Modified analog from MOTS-c biology | Small completed Phase 1a/1b | Different molecule — data do not transfer |
| Elamipretide (SS-31) | Binds cardiolipin at inner mitochondrial membrane | Multiple human trials; accelerated approval for Barth syndrome | Different mechanism; approved dose must not be borrowed |
| Humanin | Different mitochondrial-derived cytoprotective signaling | Mostly biomarker and preclinical | Distinct sequence and pathways |
| Metformin | Hepatic glucose output; energy-sensing pathways | Extensive randomized and real-world evidence | Approved oral drug — not interchangeable |
| Exercise | Multisystem adaptation | Extensive human evidence | May raise endogenous MOTS-c; not reducible to one peptide |
MOTS-c Clinical Evidence
Key published and registered programs. Keep native MOTS-c, endogenous measurements, genetics, and CB4211 in separate evidence lanes.
Discovery and metabolic characterization (Lee 2015)
Design: Cell experiments and multiple mouse metabolic models · Main result: AMPK-linked metabolic effects, reduced HFD weight gain, improved insulin sensitivity · Limit: Preclinical — no administered-human outcome
Exercise, physical performance, and aging (Reynolds 2021)
Human arm: Endogenous MOTS-c rose after exercise in 10 men · Mouse arm: Administered MOTS-c improved treadmill performance · Limit: Human component did not test MOTS-c as a drug
CB4211 Phase 1a/1b (NCT03998514)
Compound: Modified analog · Phase 1b: 25 mg SC daily × 4 weeks in obesity/NAFLD · Sponsor result: Lower ALT/AST/glucose; liver fat similar to placebo · Limit: Different molecule, small sample, exploratory endpoints
Evidence Quality
| Evidence type | Strength | Current assessment |
|---|---|---|
| Native MOTS-c randomized human trials | Very low / pending | One recruiting Phase 2a; no results |
| Native MOTS-c human dose and PK | Absent | Fixed trial dose undisclosed; no published PK |
| Human endogenous physiology | Low to moderate for association | Exercise-responsive findings, but small studies |
| Human genetic evidence | Moderate for biological relevance | Association does not prove treatment benefit |
| CB4211 analog trial | Low for MOTS-c | Informative but not transferable |
| Animal intervention studies | Moderate for preclinical plausibility | Multiple models; limited translation |
| FDA approval | None | MOTS-c is not approved |
The correct evidence label is preclinical with early human translational research and one ongoing randomized trial — not “clinically proven.”
Regulatory and Research Status
Is MOTS-c FDA approved? No. It is not approved to treat obesity, insulin resistance, diabetes, fatigue, osteoporosis, muscle loss, aging, or any other condition.
On July 23, 2026, PCAC voted 7–5 with two abstentions to recommend 503A-list inclusion despite FDA staff recommending against it. That vote is advisory and nonbinding — not drug approval and not automatic nationwide compounding authorization.
- WADA: Prohibited at all times under S4.4.1 as an AMPK activator.
- Outside the U.S.: FDA’s 2026 review reported no authorized MOTS-c products on the EMA website.
- “Research use only” labeling does not verify identity, sterility, purity, or suitability for injection.
Regulatory timeline
Discovery → WADA → MOTS-MET → nonbinding 2026 PCAC vote
2015
Discovery paper
ScienceLee et al. report MOTS-c as a mitochondrial-derived metabolic signal.
2021
CB4211 analog topline
AnalogPhase 1a/1b sponsor results for modified analog — not native MOTS-c.
2024
WADA listing
Anti-dopingExplicit prohibition as AMPK activator under S4.4.1 (in and out of competition).
Feb 2026
MOTS-MET study start
Clinical trialFirst registered randomized native-MOTS-c metabolic efficacy trial begins recruiting.
Jun 2026
Stromal-cell repair paradox
ScienceAMPK activation with reduced proliferation, ↑ p16/p21/TNF-α, impaired reparative function.
Jul 2026
FDA / PCAC compounding review
Compounding processStaff recommended against 503A listing; PCAC voted 7–5 (2 abstentions) for inclusion — nonbinding.
Pending
FDA final action & MOTS-MET results
FDA approval: noneFinal compounding determination and Phase 2a outcomes still pending.
Separate badges: FDA approval = none · clinical trial = recruiting · compounding-list process = pending · anti-doping = prohibited always.
Frequently Asked Questions
What is MOTS-c?
MOTS-c is a naturally occurring 16-amino-acid signaling peptide encoded within mitochondrial DNA. It is being studied for roles in cellular energy sensing, metabolic stress, skeletal-muscle function, and aging biology.
What is the MOTS-c dosage?
There is no established or FDA-approved human MOTS-c dose. The active Phase 2a trial uses a fixed once-daily subcutaneous dose but does not disclose the amount publicly.
Why do websites recommend 5 mg or 10 mg?
Five- and ten-milligram strengths are widely repeated commercial protocols and were also proposed vial strengths in a withdrawn compounding nomination. They are not validated by completed native-MOTS-c clinical trials or approved labeling.
Does MOTS-c require dose escalation?
No evidence-based MOTS-c escalation schedule exists. The public Phase 2a registry describes a fixed dose and does not list titration.
Is MOTS-c FDA approved?
No. MOTS-c is not FDA approved for any medical condition.
Did the FDA approve MOTS-c compounding in 2026?
No. An FDA advisory committee recommended possible 503A-list inclusion in July 2026, but the recommendation was nonbinding and did not itself change the law, approve a drug, or authorize nationwide compounding.
Is MOTS-c safe?
Human safety is not established. There are no published adverse-event rates from a completed native-MOTS-c intervention trial, and FDA has highlighted gaps in immunogenicity, impurities, aggregation, toxicity, and human exposure data.
Does MOTS-c help with weight loss?
MOTS-c reduced high-fat-diet weight gain in mice, but human weight-loss efficacy has not been demonstrated. The ongoing Phase 2a trial has no results yet.
Does MOTS-c build muscle?
There is no evidence that administered MOTS-c builds muscle in humans. Cell and mouse studies report lower myostatin and reduced atrophy signaling — not demonstrated human hypertrophy or strength gain.
Is MOTS-c an exercise mimetic?
It is described as an exercise mimetic in preclinical research because it overlaps with some exercise-responsive pathways. It does not reproduce the full benefits of exercise and has not been shown to replace training in humans.
What is the half-life of MOTS-c?
The human in-vivo half-life is unknown. FDA identified no in-vivo pharmacokinetic study; an in-vitro human-blood experiment showed rapid peptide cleavage but cannot define a clinical half-life.
Is CB4211 the same as MOTS-c?
No. CB4211 is a modified analog. Its 25 mg dose, liver-enzyme findings, injection-site reactions, and pharmacokinetics cannot be assigned to native MOTS-c.
Is MOTS-c banned in sports?
Yes. WADA prohibits MOTS-c at all times as an AMPK activator under Section S4.4.1.
Can MOTS-c be combined with GLP-1 drugs, metformin, NAD+, or other peptides?
No controlled human studies establish the safety, dosing, or benefit of those combinations. Mechanistic overlap or online “stack” descriptions are not evidence of compatibility or synergy.
References
Lee C, et al.
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasisCell Metab. 2015.
Reynolds JC, et al.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical declineNat Commun. 2021.
Kim KH, et al.
MOTS-c translocates to the nucleus to regulate nuclear gene expressionCell Metab. 2018.
Zhou Q, et al.
Mitochondrial-derived peptide and metabolic states: systematic review and meta-analysisDiabetol Metab Syndr. 2024.
ClinicalTrials.gov
MOTS-MET: MOTS-c for insulin sensitivity in prediabetesNCT07505745 — recruiting.
ClinicalTrials.gov
CB4211 Phase 1a/1bNCT03998514 — modified analog.
U.S. FDA
Evaluation of MOTS-c-related bulk drug substances (July 2026 PCAC)FDA briefing document.
WADA
2026 Prohibited ListS4.4.1 AMPK activators include MOTS-c.
Xing L, et al.
MOTS-c activates metabolic signaling but blunts reparative function in human MSCsInflamm Regen. 2026.
Important Safety Information
MOTS-c is an investigational mitochondria-derived peptide. It is not FDA approved, has no established human dosage, and has no published completed native-MOTS-c adverse-event profile.
CB4211 is a modified analog — its dose and safety data must not be assigned to native MOTS-c. Online 5–10 mg protocols are not validated clinical doses.
MOTS-c is prohibited at all times by WADA as an AMPK activator. This page is an evidence reference — not a dosing, reconstitution, or stack guide.