Dashnaiv Peptides
Compounds·mitochondrial peptides·mitochondria-derived; AMPK and folate-cycle effects reported

MOTS-c: what the mouse studies show, why no human has been given it, side effects, and its status

What 277 indexed publications and 4 randomized trials actually state about mots-c, sentence by sentence, each tied to its source and labeled by the kind of evidence it is.

Human clinical trial Reviewed 45 sources Updated

At a glance

Evidence availability
Human clinical evidence
Strongest tier in the indexed literature
Indexed publications
277
Europe PMC, title or abstract, 2026-09-14
Human studies in ledger
13
3 randomized; study count, not efficacy proof
Approval
none found
no registered development programme
Routes reported
intraperitoneal, intravenous, subcutaneous
from studies in this ledger
Studied in
Humans, Mice, Rats
25 primary studies in the evidence table
Reviewed by Adam Mirando, PharmD, on . What changed

What MOTS-c is and how it acts

MOTS-c is a peptide in the mitochondrial peptides class (mitochondria-derived; AMPK and folate-cycle effects reported). Europe PMC indexes 277 publications naming it or a listed alias in a title or abstract, including 4 randomized controlled trials and 1 clinical trials of any design, as of . The strongest evidence tier in that literature is human clinical trials.

This page reports what those studies state, sentence by sentence, with each statement tied to its source and labeled by the kind of evidence it is. It does not recommend use, and it does not translate study doses into anything personal.

What the evidence level means

Publication counts show what is indexed, not how strong the evidence is. The ledger below separates human clinical records from preclinical, analytical, and in-vitro work.

Human clinical studies in this ledger133 randomized · 10 other human clinical
Evidence strengthNot yet assessedSeparate from evidence availability
Efficacy signalNot yet assessedRead the study result, not the tier alone

Interpretation boundary: An indexed publication count is a discovery measure. It does not establish efficacy, safety, approval, or a personal treatment plan.

MOTS-c in two minutes

What it is. A small peptide made by mitochondria themselves, released with exercise and metabolic stress, that activates the cell's energy sensor and shifts metabolism toward burning fat and taking up glucose.

What the research actually shows. 277 indexed publications. Mice: better insulin sensitivity, resistance to diet-induced obesity, better late-life fitness. People: circulating levels rise with exercise and track metabolic health in observational studies. No human has been given MOTS-c in a trial; a synthetic analogue completed phase 1 and was dropped.

Status. Not approved anywhere; prohibited at all times under WADA S4.4 as an AMPK activator, per USADA.

Where the evidence is thinnest. Any effect of administering it to a person, at any dose, for anything.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

How MOTS-c works

Written from general pharmacology and the development record, and marked as editorial synthesis; the measurements behind it are quoted in the biomarker section.

  • MOTS-c is a 16-amino-acid peptide encoded not in the cell nucleus but in the mitochondrial genome, within the gene for the 12S ribosomal RNA. Its discovery in 2015 was one of the first demonstrations that mitochondria make signalling peptides of their own. It is released in response to metabolic stress and exercise, and it can move into the nucleus to alter gene expression.Editorial synthesis
    Editorial synthesis from general knowledge
  • Its proposed actions are activation of AMPK, the cell's energy sensor, and modulation of the folate and one-carbon cycle, which together shift cells toward glucose uptake and fat oxidation. In mice, MOTS-c improved insulin sensitivity, prevented diet-induced obesity and fat accumulation, and, given to old mice, improved physical capacity; in one widely cited study, late-life treatment roughly doubled running performance. A common variant of the gene, more frequent in East Asian populations, has been associated with longevity in observational studies.Editorial synthesis
    Editorial synthesis from general knowledge
  • In people the evidence is observational: circulating MOTS-c rises with exercise, differs between groups with and without conditions such as polycystic ovary syndrome, hypertension or kidney disease, and correlates with measures of metabolic and vascular health. No trial has administered MOTS-c to people. A synthetic analogue, CB4211, completed a phase 1 study in obesity and fatty liver before its developer discontinued the programme.Editorial synthesis
    Editorial synthesis from general knowledge

What did the studies find?

Reported outcomes in mice and observational associations in people; no human has been given MOTS-c. One row per primary study in this record's ledger. Fields are read from each paper's indexing and abstract. "Analytical method" marks papers about detecting or measuring the compound rather than about its effects.

25 primary studies in this record's ledger, strongest evidence first. A dash means the abstract did not state the value.
StudyDesignnSpeciesDoseRouteDurationReported outcomeTier
Cuyàs 2022 Randomized controlled trial — Humans——24 weeks We failed to find any significant alteration of circulating MOTS-c -as measured using the commercially available competitive ELISA CEX132Hu- in response to 24 weeks of a neoadjuvant chemotherapy/trastuzumab regimen… Human clinical trial
Dieli-Conwright 2021 Randomized controlled trial — Humans——— Post-exercise levels of MOTS-c among non-Hispanic White BCS were significantly associated with reductions in fat mass, body weight, HOMA-IR, CRP, and an increase in lean mass (p < 0.01). Human clinical trial
von 2021 Randomized controlled trial 10 Humans——— MOTS-C levels showed a trend to increase after EE. Human clinical trial
Sonay 2026 Human study 180 Humans——— Circulating MOTS-c levels were significantly lower in patients with HT compared to controls ( p p p p Conclusions : Circulating MOTS-c levels are markedly reduced in patients with HT and are independently associated… Observational, human
Musolino 2026 Human study — Humans——— Conversely, dialysate MOTS-c (dMOTS-c) were strongly and inversely correlated with PWV (R = - 0.717, p = 0.019) as well as systolic and diastolic blood pressure (R = -0.5, p Conclusion Ηigher urinary MOTS-c was linked… Observational, human
Peng 2026 Human study 34 Humans——— The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis… Observational, human
Filibeli 2026 Human study — Humans——— The mean serum MOTS-c levels in the PCOS group were higher than in the control group; however, this difference did not reach statistical significance (p = 0.059). Observational, human
Kutuk 2026 Human study — Humans——— Women with PCOS exhibited lower circulating MOTS-c concentrations compared with controls (220.2 ± 147.6 pg/mL vs. 498.3 ± 224.4 pg/mL, p < 0.001). Observational, human
Yoon 2026 Human study 6 Humans——— Circulating MOTS-c levels were significantly higher in obese compared to lean individuals (273 ± 56 vs. 223 ± 50 pg/mL; P P = 0.035 and P = 0.032, respectively). Observational, human
Erol 2025 Human study — Humans——— Patients who responded to treatment exhibited a substantial post-therapy increase in MOTS-c levels, while refractory cases showed little to no change. Observational, human
Ozkaya 2025 Human study 85 Humans——— We found no significant difference in serum MOTS-c levels between individuals with obesity and those with normal body mass index (14.33 ± 3.76 pg/mL versus 13.67 ± 3.44 pg/mL; p = 0.395). Observational, human
Sánchez-Quintero 2025 Human study 17 Humans——— We observed significantly reduced levels of both proteins in patients, suggesting that substantial mitochondrial dysfunction occurs in AVD patients, independent of sex or age, but directly related to the disease. Observational, human
Kamiński 2024 Human study — Humans—intravenous— These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue… Observational, human
Rice 2026 Animal study — Mice——— — Animal, preclinical
Santhanam 2026 Animal study 6 Rats——— MOTS-c treatment improved post-ischemic mechanical recovery, attenuated oxidative stress, partially preserved mitochondrial enzyme activities and membrane potential, and mitigated reductions in mtDNA copy number and… Animal, preclinical
Jamnick 2026 Animal study — Mice15 mg/kgintraperitoneal— In vitro , MOTS-c increased PGC-1α mRNA (+84.6%) and AMPK phosphorylation (+103.1%). Animal, preclinical
Mills 2026 Animal study — Rats——— MOTS-c treatment significantly reduced fasting blood glucose and circulating C-reactive protein levels, while selectively modulating plasma inflammatory cytokines, including interleukin (IL)-10 and IL-1β. Animal, preclinical
Li 2026 Animal study — Rats, Mice——— Key findings We found that hyperoxia exposure in neonatal mice led to significant cardiac hypertrophy, fibrosis, and dysfunction, concomitant with decreased serum MOTS-c content. Animal, preclinical
Zhang 2026 Animal study 6 Mice5 mg/kgintraperitoneal2 weeks Mechanistically, R13A-MOTS-c activated the Nrf2 signaling pathway, as evidenced by increased nuclear translocation of Nrf2 and upregulation of its downstream targets gene. Animal, preclinical
Liao 2026 Animal study 36 Rats, Mice——— In vivo, HNG or MOTS-c treatment reduced AF inducibility and attenuated AngII-induced atrial fibrosis and hypertrophy. Animal, preclinical
Blatkiewicz 2026 Animal study 16 Rats—subcutaneous— MOTS-c showed significantly higher expression in ZF/ZR vs. ZG. Animal, preclinical
Li 2026 Animal study — Rats——— Both approaches led to marked enhancements in glucose and lipid metabolism, lowered collagen buildup, and bettered both systolic and diastolic heart functions. Animal, preclinical
Santhanam 2026 Animal study — Rats0.25-0.7 mg/kg; 0.5 mg—— Lactate dehydrogenase release decreased by 65%. Animal, preclinical
Güvenir 2026 Animal study — Rats—intraperitoneal— Valproic acid exposure led to impaired sociability, repetitive behaviors, anxiety, cerebellar Purkinje cell loss, and increased oxidative stress and neuronal damage in the prefrontal cortex. Animal, preclinical
Li 2026 Animal study 6 Mice—intraperitoneal— Furthermore, MOTS-c treatment significantly restored GSH content, diminished reactive oxygen species (ROS) production, and oxidative stress. Animal, preclinical

Doses reported in studies

Each entry is a sentence quoted from the study's abstract, with the study's design, sample size and year in front of it. Comparator doses in the same sentence are not attributed to mots-c.

  • Animal study mice 2026 Animal, preclinical
    Doses stated in the abstract: 15 mg/kg
    In vivo , male mice were inoculated with Colon-26 (C26) carcinoma cells and treated daily with MOTS-c (15 mg/kg/2x Day, i.p.) or vehicle.
    Source pmid-42266945 · quoted verbatim from the abstract, emphasis added
  • Animal study mice n = 6 2026 Animal, preclinical
    Doses stated in the abstract: 5 mg/kg
    In vivo studies demonstrated that daily intraperitoneal administration of R13A-MOTS-c (5 mg/kg for 2 weeks) effectively mitigated radiation-induced pulmonary inflammation, oxidative stress, and mitochondrial dysfunction in C57BL/6 mice exposed to 20 Gy thoracic irradiation.
    Source pmid-42142418 · quoted verbatim from the abstract, emphasis added
  • Animal study rats 2026 Animal, preclinical
    Doses stated in the abstract: 0.25-0.7 mg/kg; 0.5 mg
    Isolated Langendorff-perfused rat hearts underwent 30-min global ischemia and 60-min reperfusion with or without MOTS-c (0.25-0.7 mg/kg) delivered via Krebs-Henseleit buffer during the first 10 min of reperfusion.
    Source pmid-41593376 · quoted verbatim from the abstract, emphasis added
  • Animal study rats 2025 Animal, preclinical
    Doses stated in the abstract: 15 mg/kg
    Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
    Source pmid-40661667 · quoted verbatim from the abstract, emphasis added
  • Animal study mice 2021 Animal, preclinical
    Doses stated in the abstract: 500 μg
    Long-term repeated administration of MOTS-c (500 μg) and PMO at the dose of 12.5 mg/kg/week for 3 weeks followed by 12.5 mg/kg/month for 3 months (PMO-M) induced therapeutic levels of dystrophin expression in peripheral muscles, with up to 25-fold increase in diaphragm of mdx mice over PMO alone.
    Source pmid-33337582 · quoted verbatim from the abstract, emphasis added

MOTS-c doses in studies

Every administered dose is in mice. Human studies measured the body's own MOTS-c; they gave none.

StudyDose and routeDurationFinding
Mouse metabolic studies5 to 15 mg/kg intraperitoneal, dailyDays to weeksImproved insulin sensitivity; less fat gain; PGC-1α and AMPK activation
Old mice, late-life treatmentIntraperitoneal, intermittentWeeksImproved running capacity and healthspan measures
Rat heart injury modelIntraperitonealDaysBetter post-ischaemic recovery; less oxidative stress
Human observational studiesNone given; blood levels measuredCross-sectional or exercise sessionsLevels rise with exercise; differ by condition
CB4211 analogue, phase 1Not published in this ledgerWeeksSafety study in obesity and fatty liver; development stopped

Figures for this compound circulate on forums and vendor pages. None has been tested in a human study, so none is reproduced here; the table above holds every dose a study actually administered.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Adverse events and frequency

Events and their frequency as each study reported them, with the denominator where the abstract gives one.

  • Human study humans n = 34 2026 Observational, human
    The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade and adverse event incidence (all p p Conclusions : Postoperative peripheral serum MOTS-c levels represent an independent protective factor against MIRI in patients with acute myocardial infarction and suggest a potential predictive value for MIRI, although its clinical utility as a standalone predictor requires further validation through dynamic monitoring and larger-scale studies.
    Source pmid-42072458 · quoted verbatim from the abstract

Who MOTS-c is discussed for, and the cautions that recur

The interest. Fat loss, exercise capacity, insulin resistance and ageing, each of which has a mouse result behind it.

  • Blood sugar medication. The compound improves glucose uptake in mice; combined with insulin or other glucose-lowering drugs the effect is unstudied.
  • Cancer. Metabolic reprogramming and AMPK activation cut both ways in tumour biology; untested.
  • Athletes. An AMPK activator, within WADA's prohibited metabolic-modulator class.
  • Flushing. The most consistent community report; its mechanism is unknown.
  • Pregnancy, children. No data.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Biomarkers measured in studies

Laboratory and clinical measures the studies report tracking, including which hormones did and did not change.

  • Randomized controlled trial humans 2022 Human clinical trial
    MOTS-c mechanisms of action (MoA) involve insulin sensitization, enhanced glucose utilization, suppression of mitochondrial respiration, and targeting of the folate-AICAR-AMPK pathway.
    Source pmid-36490309 · quoted verbatim from the abstract
  • Randomized controlled trial humans 2021 Human clinical trial
    We conducted a secondary analysis of the effects of a 16-week aerobic and resistance exercise intervention on MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors (BCS).
    Source pmid-34413391 · quoted verbatim from the abstract
  • Randomized controlled trial humans n = 10 2021 Human clinical trial
    Plasma concentration of HN and MOTS-c, skeletal muscle MOTS-c as well as gene expression of exercise-related genes were analyzed.
    Source pmid-34351816 · quoted verbatim from the abstract
  • Human study humans n = 180 2026 Observational, human
    Mitochondria-derived peptides (MDPs), particularly mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c), have emerged as key regulators of cellular metabolism, insulin sensitivity, oxidative stress, and inflammatory responses.
    Source pmid-42278864 · quoted verbatim from the abstract
  • Human study humans 2026 Observational, human
    MOTS-c, a mitochondria-derived peptide, is emerging as a key regulator of skeletal muscle health, metabolic homeostasis, and vascular function, yet its role in the uremic environment remains unexplored.
    Source pmid-42126770 · quoted verbatim from the abstract
  • Human study humans n = 34 2026 Observational, human
    The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade and adverse event incidence (all p p Conclusions : Postoperative peripheral serum MOTS-c levels represent an independent protective factor against MIRI in patients with acute myocardial infarction and suggest a potential predictive value for MIRI, although its clinical utility as a standalone predictor requires further validation through dynamic monitoring and larger-scale studies.
    Source pmid-42072458 · quoted verbatim from the abstract

Reported interactions

Sentences in which the compound is studied alongside another agent. Read the quotation: the word interaction can also be statistical.

  • Randomized controlled trial humans 2022 Human clinical trial
    Here, we measured circulating MOTS-c in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin.
    Source pmid-36490309 · quoted verbatim from the abstract
  • Animal study rats, mice 2026 Animal, preclinical
    Key findings We found that hyperoxia exposure in neonatal mice led to significant cardiac hypertrophy, fibrosis, and dysfunction, concomitant with decreased serum MOTS-c content.
    Source pmid-42128272 · quoted verbatim from the abstract
  • Animal study rats 2026 Animal, preclinical
    Molecular docking demonstrated high-affinity interactions of MOTS-c with MAPK, mTOR, AMPK, NRF2, PI3K, and caspase 3.
    Source pmid-41593376 · quoted verbatim from the abstract

Reported timelines

Onset, peak and duration figures as each study reported them.

  • Animal study rats n = 6 2026 Animal, preclinical
    MOTS-c (53 µM) was administered either before ischemia or at reperfusion onset.
    Source pmid-42228044 · quoted verbatim from the abstract

What is measured over time, and what is not

In mice, metabolic changes appeared over days to weeks of dosing. In people, the body's own MOTS-c rises within an hour of exercise and falls back. Nothing has been measured after administering it to a person.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Study durations

Treatment and follow-up periods as stated in each abstract.

  • Randomized controlled trial humans 2022 Human clinical trial
    Durations stated: 24 weeks
    We failed to find any significant alteration of circulating MOTS-c -as measured using the commercially available competitive ELISA CEX132Hu- in response to 24 weeks of a neoadjuvant chemotherapy/trastuzumab regimen with or without daily metformin.
    Source pmid-36490309 · quoted verbatim from the abstract, emphasis added
  • Animal study mice n = 6 2026 Animal, preclinical
    Durations stated: 2 weeks
    In vivo studies demonstrated that daily intraperitoneal administration of R13A-MOTS-c (5 mg/kg for 2 weeks) effectively mitigated radiation-induced pulmonary inflammation, oxidative stress, and mitochondrial dysfunction in C57BL/6 mice exposed to 20 Gy thoracic irradiation.
    Source pmid-42142418 · quoted verbatim from the abstract, emphasis added
  • Animal study rats 2025 Animal, preclinical
    Durations stated: 7 day
    After the end of the experiment, we conducted an ex vivo fatigue test of soleus muscle and showed that the MOTS-c administration prevents increased fatigue during 7-day hind limb unloading.
    Source pmid-40608240 · quoted verbatim from the abstract
  • Animal study rats 2025 Animal, preclinical
    Durations stated: 3 weeks
    Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
    Source pmid-40661667 · quoted verbatim from the abstract, emphasis added
  • Animal study mice 2021 Animal, preclinical
    Durations stated: 3 weeks; 3 months
    Long-term repeated administration of MOTS-c (500 μg) and PMO at the dose of 12.5 mg/kg/week for 3 weeks followed by 12.5 mg/kg/month for 3 months (PMO-M) induced therapeutic levels of dystrophin expression in peripheral muscles, with up to 25-fold increase in diaphragm of mdx mice over PMO alone.
    Source pmid-33337582 · quoted verbatim from the abstract, emphasis added

Routes used in the studies

Routes of administration named in each study.

  • Human study humans 2024 Observational, human
    administration by intravenous route reported
    Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex.
    Source pmid-39201408 · quoted verbatim from the abstract
  • Animal study mice 2026 Animal, preclinical
    administration by intraperitoneal route reported
    In vivo , male mice were inoculated with Colon-26 (C26) carcinoma cells and treated daily with MOTS-c (15 mg/kg/2x Day, i.p.) or vehicle.
    Source pmid-42266945 · quoted verbatim from the abstract
  • Animal study mice n = 6 2026 Animal, preclinical
    administration by intraperitoneal route reported
    In vivo studies demonstrated that daily intraperitoneal administration of R13A-MOTS-c (5 mg/kg for 2 weeks) effectively mitigated radiation-induced pulmonary inflammation, oxidative stress, and mitochondrial dysfunction in C57BL/6 mice exposed to 20 Gy thoracic irradiation.
    Source pmid-42142418 · quoted verbatim from the abstract
  • Animal study rats n = 16 2026 Animal, preclinical
    administration by subcutaneous route reported
    Adult male Wistar rats (n = 16) received continuous MOTS-c (0.1 μmol/24 h) or saline via subcutaneous micro-osmotic pumps for 24 hours.
    Source pmid-41811086 · quoted verbatim from the abstract
  • Animal study rats 2026 Animal, preclinical
    administration by intraperitoneal route reported
    Female and male offspring were treated with 0.5 mg/kg/day MOTS-c or saline intraperitoneally from postnatal days 21 to 46.
    Source pmid-41706383 · quoted verbatim from the abstract
  • Animal study mice n = 6 2026 Animal, preclinical
    administration by intraperitoneal route reported
    Administration of MOTS-c via i.p. injection markedly attenuated APAP-induced increases in AST and ALT levels, histopathological liver damage, and other liver injury markers.
    Source pmid-41764620 · quoted verbatim from the abstract

Weight-normalized doses, as published

Per-kilogram figures exactly as each study published them, for the species it studied.

  • Animal study mice 2026 Animal, preclinical
    Weight-normalized doses as published: 15 mg/kg
    In vivo , male mice were inoculated with Colon-26 (C26) carcinoma cells and treated daily with MOTS-c (15 mg/kg/2x Day, i.p.) or vehicle.
    Source pmid-42266945 · quoted verbatim from the abstract, emphasis added
  • Animal study mice n = 6 2026 Animal, preclinical
    Weight-normalized doses as published: 5 mg/kg
    In vivo studies demonstrated that daily intraperitoneal administration of R13A-MOTS-c (5 mg/kg for 2 weeks) effectively mitigated radiation-induced pulmonary inflammation, oxidative stress, and mitochondrial dysfunction in C57BL/6 mice exposed to 20 Gy thoracic irradiation.
    Source pmid-42142418 · quoted verbatim from the abstract, emphasis added
  • Animal study rats 2026 Animal, preclinical
    Weight-normalized doses as published: 0.25-0.7 mg/kg
    Isolated Langendorff-perfused rat hearts underwent 30-min global ischemia and 60-min reperfusion with or without MOTS-c (0.25-0.7 mg/kg) delivered via Krebs-Henseleit buffer during the first 10 min of reperfusion.
    Source pmid-41593376 · quoted verbatim from the abstract, emphasis added
  • Animal study rats 2025 Animal, preclinical
    Weight-normalized doses as published: 15 mg/kg
    Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
    Source pmid-40661667 · quoted verbatim from the abstract, emphasis added

Weight-normalized figures above are reproduced exactly as each study published them, for the species it studied. Dose does not scale linearly with body mass between species: metabolic rate, clearance and receptor density differ, and regulatory guidance uses allometric, not proportional, conversion. A mg/kg figure from a rat study is a fact about that rat study and nothing else.

What people report outside the literature

What circulates in user communities and clinic marketing, reported so a reader knows the figures and their origin. None of it has been tested in a trial, and none of it is a suggestion.

  • MOTS-c circulates for fat loss, exercise performance, insulin sensitivity and longevity, injected on a weekly or several-times-weekly schedule in courses of one to two months. Reported effects are more energy in training and modest weight change; the most consistently reported side effect is flushing shortly after injection, with fatigue and injection-site reactions also mentioned. None of this comes from a human study, because no one has been given MOTS-c in a trial. Figures for this compound circulate on forums and vendor pages. None has been tested in a human study, so none is reproduced here; the table above holds every dose a study actually administered.Editorial synthesis
    Editorial synthesis from general knowledge
Method note · shared across compounds

Reconstitution mathematics

Lyophilised peptide is supplied as a mass in a vial and dissolved in a stated volume of diluent. Two figures follow from that and nothing else:

  • Concentration = mass in vial ÷ diluent volume. A 5 mg vial in 2 mL is 2.5 mg/mL, or 2,500 mcg/mL.
  • Volume for a given mass = that mass ÷ concentration. 250 mcg at 2,500 mcg/mL is 0.1 mL. On a U-100 insulin syringe, where 1 mL is 100 units, that is 10 units.

Study doses on this page are quoted as published, in the units the authors used. Converting between mcg, mg and IU, or between a mass and a syringe volume, is arithmetic; deciding a mass is not, and this page does not do it. The reconstitution calculator performs the conversion with the formula shown.

Method note · shared across compounds

Reading a certificate of analysis

A certificate of analysis is a laboratory report on one batch. Reading it means checking four things in order.

  1. Identity. Mass spectrometry should report an observed molecular mass matching the peptide's theoretical mass within the instrument's stated tolerance. A certificate with no mass spectrometry, or one that lists only the expected value, has not confirmed identity.
  2. Purity. HPLC purity is the area of the main peak as a share of all peaks, at a stated wavelength. It says nothing about what the other peaks are, and it is not a measure of quantity.
  3. Quantity. Net peptide content, by amino acid analysis or UV, is the fraction of the vial's mass that is peptide rather than counter-ions and water. A 5 mg vial at 80% net content holds 4 mg of peptide, and every concentration figure above changes accordingly.
  4. Provenance. The batch number on the certificate should match the vial, the laboratory should be named and independent of the seller, and the test date should be recent.

This page rates no supplier and links to none. It describes how to read the document.

Method note · shared across compounds

Equipment described in studies

Published human studies of injectable peptides report the same small set of materials: single-use insulin syringes with fixed needles, most often U-100 with 29 to 31 gauge needles; bacteriostatic water or sterile water for injection as diluent, with the choice stated in the methods; alcohol swabs; and refrigerated storage of reconstituted solution. Animal studies more often report intraperitoneal or intragastric administration and state the vehicle used. Where a study in this record's ledger names its materials or vehicle, that sentence appears under storage or routes above; where it does not, nothing is assumed here.

Storage and handling

Powder refrigerated or frozen away from light; reconstituted solution refrigerated and used within about four weeks. Discard cloudy or discoloured solution.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

What the human studies measured

They measured the peptide, not its effects. What follows is what an observational study of MOTS-c typically records.

MeasureWhyWhen
Circulating MOTS-cThe variable under study; rises with exerciseBefore and after exercise, or once
Fasting glucose, insulin, HbA1cAssociations with metabolic healthOnce
Body composition, fitnessCorrelates in cross-sectional workOnce
Blood pressure, vascular stiffnessInverse correlations reported in kidney and hypertension cohortsOnce

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Common mistakes in how MOTS-c is discussed

  • Reading observational human studies as treatment trials. They measured levels; nobody was given the peptide.
  • Reading the mouse fitness study as human anti-ageing evidence. It was mice, by injection, at doses per kilogram far above anything people use.
  • Citing CB4211 as MOTS-c safety data. A different molecule, phase 1 only, and the programme ended.
  • Calling it "natural" as if that settles safety. The body makes it in picograms; injected milligrams are a different exposure.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

MOTS-c vs SS-31 and humanin

The three mitochondrial peptides in this reference.

PeptideOrigin and mechanismHuman evidenceStatus
MOTS-cMitochondrially encoded; AMPK, one-carbon cycleObservational only; analogue in phase 1Not approved
SS-31 (elamipretide)Synthetic; binds cardiolipin in the inner membranePhase 2 and 3 trials in mitochondrial diseaseNot approved; regulatory review in Barth syndrome
HumaninMitochondrially encoded; cytoprotectiveObservational; analogues in animalsNot approved

Class records: SS-31, humanin; the mitochondrial peptides class page lists them together. The retatrutide + MOTS-c stack page covers a combination that no study has tested.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Other compounds in its class

Same class in the registry: Humanin, SS-31. Each row shows what that compound's own record states; nothing is inferred across rows.

3 compounds in the mitochondrial peptides class. Each row states what that compound's own record says; nothing is inferred across rows.
CompoundTierPublicationsRCTsRecord
MOTS-c Human clinical trial 277 4 draft
Humanin Human clinical trial 589 5 draft
SS-31 Approved label 493 16 draft

Studied in combination

Whether any indexed study tested MOTS-c together with the compounds it is commonly combined with. A count of zero is the finding, not a gap in this page.

Regulatory status

Registry facts only. Jurisdiction-level status, compounding categories and sport prohibitions need their own cited documents before they appear here.

  • U.S. Anti-Doping Agency: MOTS-c is prohibited at all times under WADA section 4.4 (metabolic modulators), 4.4.1 activators of AMP-activated protein kinase.Approved label
    Source usada-mots-c
  • U.S. Anti-Doping Agency: not FDA-approved for use in humans or in compounded medications; no completed human clinical trials.Approved label
    Source usada-mots-c
  • The synthetic analogue CB4211 completed a phase 1 study in obesity and fatty liver before its developer discontinued the programme; MOTS-c itself has never been administered to people in a registered trial.Editorial synthesis
    Editorial synthesis from general knowledge

Open questions and limitations

What is genuinely unknown, stated plainly. A missing field is not evidence that the outcome is safe, effective, or established.

  • No study in this record's ledger reports dose-escalation schedules for MOTS-c.
  • No study in this record's ledger reports exclusion criteria for MOTS-c.

Questions people ask

What are the side effects of MOTS-c?

Unknown in people. Community reports describe flushing after injection most consistently, plus fatigue and injection-site reactions.

What is MOTS-c?

A 16-amino-acid peptide encoded in the mitochondrial genome, released with exercise and metabolic stress, that activates AMPK and shifts cells toward burning fat and taking up glucose.

What does MOTS-c do?

In mice it improves insulin sensitivity, prevents diet-induced obesity and improves late-life fitness. In people, circulating levels rise with exercise and track metabolic health; no trial has given it to anyone.

Has MOTS-c been tested in humans?

Not by administration. Human studies measured the body's own MOTS-c. A synthetic analogue, CB4211, completed phase 1 before development stopped.

Is there a MOTS-c dose?

No human dose has been studied. Mice received milligrams per kilogram by injection; figures that circulate for people are untested and not reproduced here.

What are the side effects of MOTS-c?

Unknown in people. Community reports describe flushing after injection most consistently, plus fatigue and injection-site reactions.

Why does MOTS-c cause flushing?

Unknown. It is the most consistent community report and no study has examined it.

Is MOTS-c FDA approved?

No, and it has never been administered to people in a registered trial.

Is MOTS-c banned in sport?

Yes. USADA states it is prohibited at all times under WADA section 4.4, metabolic modulators, as an activator of AMPK.

Does MOTS-c help with weight loss?

In mice it prevents fat gain on a high-fat diet. No human study has measured weight change after administration.

Does MOTS-c improve exercise performance?

In old mice, late-life treatment improved running capacity. In people, the body's own MOTS-c rises with exercise; no one has tested giving it.

What is MOTS-c's half-life?

Not measured in people after administration. The body's own levels rise and fall around exercise within hours.

MOTS-c vs SS-31: what is the difference?

Both act on mitochondria, but SS-31 is a synthetic peptide with phase 2 and 3 trials in mitochondrial disease, while MOTS-c is a natural mitochondrial peptide with no human administration studies.

Is MOTS-c linked to longevity?

A common variant of its gene, more frequent in East Asian populations, is associated with longevity in observational studies. Association is not effect, and no trial exists.

How should MOTS-c be stored?

Powder refrigerated or frozen away from light; reconstituted solution refrigerated and used within about four weeks.

What is CB4211?

A synthetic MOTS-c analogue developed by CohBar that completed a phase 1 study in obesity and fatty liver; the company discontinued it.

How many MOTS-c studies exist?

277 indexed publications; 25 primary studies are tabulated here, 13 of them human and all of those observational.

Sources

Full citations. Every claim above links to one of these by its id.

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    Redefining Mitochondrial Therapy for ME/CFS: The Case for MOTS-c
    doi-10-20944-preprints202507-0058-v2 · · preprint
  16. 28
  17. 29
    Redefining Mitochondrial Therapy for ME/CFS: The Case for MOTS-c
    doi-10-20944-preprints202507-0058-v1 · · preprint
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    Mitochondria-derived peptides in aging and healthspan.
    pmid-35499074 · · peer-reviewed
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  29. 41
    Mitochondrial-derived peptides in energy metabolism.
    pmid-32776825 · · peer-reviewed
  30. 42
  31. 43
    Mitochondrially derived peptides as novel regulators of metabolism.
    pmid-28574175 · · peer-reviewed
  32. 44
  33. 45

Reference card

Reference card · generated /compounds/mots-c
Compound
MOTS-c, mitochondrial peptides
Evidence tier
Human clinical trial
Indexed publications
277 · 4 RCTs · 1 other clinical trials
Approval
no registered development programme found
Routes reported
intraperitoneal, intravenous, subcutaneous
Reviewed
Adam Mirando, PharmD,

Study figures are as published in each source and are not recommendations. Print or save this card with its date.

Last reviewed and what changed

Newest first. These are the record's own revision dates, and the same dates feed the sitemap.

  1. · Reviewed by Adam Mirando, PharmD, on 2026-09-25.
  2. · Misattribution check: study_durations (pmid-40496439): the quoted schedule is for FGF21, semaglutide and an amylin analogue; MOTS-c was not the treatment. The sources stay in the ledger; only the claims that put another agent's result under this compound were removed.
  3. · USADA added to the ledger; the sport-status statement is now a verbatim regulatory claim (S4.4, prohibited at all times) instead of an editorial hedge. Stage 2 competitors and information gain written to the intent map.
  4. · Written guide, FAQ to 16, mechanism, reported-use (no circulating figures reproduced) and regulatory editorial sections; the observational-versus-administered distinction made explicit; intent-driven H1 and title.
  5. · Claims drafted extractively from 40 ledger sources by scripts/draft_claims.py: 33 claims, 25 evidence-table rows. Status researched -> draft.
  6. · Claims drafted extractively from 40 ledger sources by scripts/draft_claims.py: 38 claims, 25 evidence-table rows. Status researched -> draft.
  7. · Evidence fetched from Europe PMC and ChEMBL by scripts/fetch_evidence.py; claims not yet written.