MOTS-c
Mitochondrial-derived peptide · metabolic & exercise biology
MOTS-c is a 16-amino-acid peptide your mitochondria make from their own DNA. It switches on AMP-activated protein kinase (AMPK), the cell's master metabolic switch. People run it for insulin sensitivity, body composition and exercise capacity. Exercise raises your own MOTS-c, so people pair the two.
Buy MOTS-c20 mg vial
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At a glance
- Dose
- 500–1,000 mcg a day (250–500 mcg to start)
- How often
- Once daily, or near-daily
- How
- A small injection under the skin
- When
- Morning, or 30 to 60 minutes before training
- Cycle
- 8–12 weeks on, then a 4–6 week break
The 30-second versionEverything on this page, fast
Mitochondrial Peptide · Exercise Mimetic · Insulin Sensitivity · Longevity
The 'exercise in a vial' peptide. MOTS-c switches on AMPK, the cell's master metabolic switch, to improve insulin sensitivity and boost exercise capacity, even in old age. Exercise raises your *own* MOTS-c, so people pair it with training.
The basics
- A 16-amino-acid peptide encoded inside your mitochondrial DNA, one of a small class called 'mitochondrial-derived peptides.'
- Studied for metabolism, insulin sensitivity, and exercise biology; run as a subcutaneous injection.
Why people use it
- More exercise capacity at any age. In mice it improved running and physical capacity, even in old age.
- Sharper insulin response. It switches on AMPK through the folate cycle and improves insulin-stimulated glucose uptake.
- Leaner body composition. On a high-fat diet, it blocked the weight gain and insulin resistance the diet usually causes.
- Daytime energy and drive. Its AMPK signal is energizing, so people run it in the active part of the day.
Stacks well with
- NAD+ is the most direct partner. MOTS-c sends the metabolic signal and NAD+ is the fuel the mitochondria run on.
- SS-31 adds membrane protection. It guards the inner mitochondrial membrane while MOTS-c drives the AMPK signal.
Good to know
- Training is the proven way to raise your own MOTS-c, so people run the peptide alongside it.
- WADA names MOTS-c on its prohibited list, so check before you compete.
What it does
The mitochondrial peptide, an injectable take on the metabolic side of exercise.
- More exercise capacity at any ageOld mice dosed daily for 2 weeks ran 2 times longer and 2.16 times farther than untreated old mice.
- Sharper insulin responseIn mice, 7 days of dosing raised whole-body insulin sensitivity about 30% on the reference clamp test.
- Leaner body compositionOn a 60% fat diet for 8 weeks, treated mice gained much less weight and had far less liver fat.
- Held onto muscle through forced restWith both hind legs cast for 8 days, mice lost about 15% of muscle mass. Treated mice lost 5%.
- More MOTS-c, less myostatin in peopleIn 105 Japanese men, higher blood MOTS-c ran with lower myostatin, the brake on muscle growth.
Sources:PMID 25738459PMID 33473109PMID 38170165PMID 33554779
How it works
Made by your mitochondria. MOTS-c, first described in 2015, is a 16-amino-acid peptide encoded by a short reading frame inside the mitochondrial 12S rRNA gene, not the main genome. That makes it one of a class called mitochondrial-derived peptides.
Switches on AMPK. MOTS-c interferes with the folate one-carbon cycle, which raises AICAR and activates AMP-activated protein kinase (AMPK), the cell's master energy sensor. Through that pathway it boosts insulin-stimulated glucose uptake in muscle. Under metabolic stress it also moves into the nucleus to switch on stress-response genes.
Mimics exercise. In mice, MOTS-c improved physical performance at every age. In people, exercise itself raises your own MOTS-c in muscle and blood, the same signal the peptide is built to copy.
Sources:PubChem CID 146675088PMID 25738459PMID 29983246PMID 33473109
How to dose it
Most people run MOTS-c as a small injection under the skin, once a day or near-daily.
Dose tiersMost people run 5 to 10 mg a week in daily or near-daily shots.
- Low / conservative:
- 250 to 500 mcg once a day (1.75 to 3.5 mg a week), a conservative start.
- Standard:
- 500 to 1,000 mcg once a day (3.5 to 7 mg a week), the most common range.
- Higher / metabolic focus:
- 1,000 to 1,500 mcg once a day (7 to 10 mg a week), the upper end of what people run.
- Split-dose alternative:
- 500 mcg twice a day instead of one larger shot, for steadier exposure.
How to injectA small injection into the fat under the skin, most often in the morning.
- Injection site:
- Abdomen (clear of the navel), love handles or outer thigh; rotate sites.
- Measuring the dose:
- Draw it on a U-100 syringe. The mixing card below gives the syringe units for any dose.
- Time of day:
- Morning is most common, or 30 to 60 minutes before exercise.
- Food window:
- Fasted, before breakfast, fits the metabolic angle.
Cycle and breaks8 to 12 weeks on, then a 4 to 6 week break.
- Standard cycle:
- 8 to 12 weeks of daily or near-daily use, then reassess insulin and metabolic markers.
- Washout:
- A 4 to 6 week break afterward, giving the body's signaling time to reset.
- Daily or every other day:
- Mouse metabolic studies dosed near-daily; the aging study, about 3 times a week. Both are used. On every other day (EOD), raise each shot to keep the same weekly total.
Mixing the vialA 10 mg vial with 2 mL of bacteriostatic water gives 5,000 mcg per mL.
- Mixing:
- 10 mg vial plus 2 mL bacteriostatic water makes 5,000 mcg per mL.
- On the syringe:
- 250 mcg takes 5 units, 500 mcg takes 10 units, 750 mcg takes 15 units, 1,000 mcg takes 20 units, up to a full 1 mL (100 units) syringe.
- Why 2 mL:
- Covers 250 to 1,000 mcg. For more volume, 3 mL (the vial's maximum) puts 1,000 mcg at 30 units.
Sources:PMID 25738459PMID 33473109
Best time to take it
Implied best time
Morning / pre-workout
Most people take MOTS-c in the morning, or 30 to 60 minutes before training.
- MOTS-c activates AMPK and boosts insulin sensitivity, an energizing signal that pairs naturally with daytime activity rather than an evening wind-down.
- Some people inject 30 to 60 minutes before exercise, pairing the injected signal with the body's own exercise-driven MOTS-c response.
- Dosing fasted, before breakfast, is the common choice for the metabolic and insulin-sensitivity angle.
Sources:PMID 25738459PMID 33473109
What to stack it with
MOTS-c pairs with other mitochondrial-support peptides and with NAD+ precursors that feed the same machinery.
MOTS-c + NAD+MOTS-c is the metabolic signal, NAD+ is the fuel it runs on.
- Why it works:
- AMPK activation and NAD+ feed the same longevity pathways, sirtuins and PARP repair, from different angles.
- The protocol:
- MOTS-c 500 to 1,000 mcg subcutaneously once a day, with NMN or NR 500 mg orally each morning. Some prefer injectable NAD+ 250 to 500 mg, IV or subcutaneous.
- Outcome:
- Reached for metabolic optimization, insulin sensitivity and cellular energy.
MOTS-c + SS-31SS-31 protects the mitochondrial membrane while MOTS-c drives the metabolic signal inside the mitochondria.
- Why it works:
- SS-31 protects the inner mitochondrial membrane and cuts oxidative stress; MOTS-c works on the metabolic signaling side. Together they cover structure and output.
- The protocol:
- MOTS-c 500 to 1,000 mcg subcutaneously once a day, plus SS-31 1 to 5 mg subcutaneously once a day, both run in defined cycles.
- Outcome:
- Reached for mitochondrial health and exercise capacity.
MOTS-c + HumaninHumanin adds cell protection and insulin signaling to MOTS-c's AMPK drive.
- Why it works:
- Humanin protects cells from apoptosis and improves insulin action through a different route than MOTS-c's AMPK pathway. Together they cover two mitochondrial angles.
- The protocol:
- MOTS-c 500 to 1,000 mcg subcutaneously once a day, plus humanin 2 to 4 mg subcutaneously once daily or every other day, in 8 to 12 week cycles.
- Outcome:
- Reached for longevity and metabolic flexibility, the core mitochondrial-derived peptide stack.
Support nutrients
MOTS-c is mitochondrial at its core, so the best cofactors amplify exercise, feed the machinery and support insulin sensitivity.
Raise your own MOTS-cHard cardio is one trigger research has shown.
- Why it matters:
- Hard intervals raise your own MOTS-c the same way the peptide acts, so the two work together.
- How much:
- 3 to 5 sessions a week, with hard intervals.
Where folate fits inMOTS-c switches AMPK on by lowering active folate.
- In cells:
- MOTS-c drained active folate and raised AICAR. Adding folic acid reversed its effect on their oxygen and glucose use.
Feed the mitochondriaCoQ10, B vitamins and magnesium feed the machinery MOTS-c switches on.
- CoQ10:
- 100 to 300 mg a day, with a fat-containing meal. Ubiquinol is preferred after 40 or on statins.
- B-complex:
- A daily B-complex feeds the mitochondrial fuel chain.
- Magnesium:
- 200 to 400 mg a day, glycinate or malate, in the evening, for sleep and insulin sensitivity.
Keep insulin sensitivity workingSteady blood sugar and good sleep let MOTS-c's insulin effect work.
- Why it matters:
- High blood sugar and insulin spikes blunt AMPK, the pathway MOTS-c activates. Steady glucose removes resistance to its signal.
- Diet and sleep:
- A whole-food diet with 25 to 40 g of fiber a day, and 7 to 9 hours of sleep; poor sleep worsens insulin sensitivity.
- Berberine:
- 500 mg, 2 to 3 times a day with meals. A non-peptide AMPK activator on the same lever, so it adds to MOTS-c rather than covering a new angle.
Dose calculator
Reconstitution calculator
Calculated for a 1 mL U-100 insulin syringe (100 units/mL).
Units per dose
20 units
Draw this many units on a U-100 syringe
Each unit holds 50 mcg
- Volume per dose
- 0.2 mL
- Doses per vial
- 10
- Concentration
- 5 mg/mL
One vial lasts
- Daily
- 10 days
- Every other day
- 20 days
- 5×/week
- 14 days
Research use only. Not for human consumption. Outputs are reference values based on research literature. Verify all measurements independently.
Side effects and what to watch
What studies report. Animal studies gave MOTS-c without reported overt toxicity. They were designed to test metabolic effects, not safety.
Worth knowing. The nearest human safety data come from CB4211, an analog of MOTS-c. In its Phase 1a/1b trial, injection-site reactions were the common complaint, 79% against 33% on placebo, with no serious adverse events reported.
Sources:PMID 25738459ClinicalTrials.gov NCT03998514SEC Form 8-K (CohBar, Aug 10, 2021)
Common questions
How is MOTS-c dosed?
Most people run 500 to 1,000 mcg once a day, in a range of 250 to 1,500 mcg (about 5 to 10 mg a week). Some split it into 500 mcg twice a day instead.
When should I take it?
Most people take it in the morning, or 30 to 60 minutes before training, to line the metabolic signal up with the active part of the day.
Do I need to cycle MOTS-c?
Most people run it 8 to 12 weeks, then take a 4 to 6 week break before starting again.
What does MOTS-c stack with?
The mitochondrial-derived peptides SS-31 and humanin, and NAD+ precursors like NMN or NR, which feed the same mitochondrial machinery MOTS-c signals to.
Why does exercise pair so well with MOTS-c?
In people, hard cardio intervals are one trigger research has shown. They raise your own levels the same way the injected peptide is thought to act, so running both together lines up the natural and injected signal.
How do I measure a dose from a 10 mg vial?
Mixed with 2 mL of bacteriostatic water, a 10 mg vial gives 5,000 mcg per mL. 500 mcg takes 10 units and 1,000 mcg takes 20 units on a U-100 syringe.
Deep dive
Doses used in studies · Molecular identity · References
10From the researchDoses used in studies
These are the doses used in the published cell and mouse research.
| Dose | Route | Model | Outcome | Sources: |
|---|---|---|---|---|
| 5 mg/kg/day (acute, multi-day) | Intraperitoneal (IP) | Mouse, acute metabolic study | Activated AMPK and improved glucose handling / insulin-stimulated glucose disposal | PMID 25738459 |
| 0.5 mg/kg/day (8 weeks) | Intraperitoneal (IP) | Mouse, high-fat-diet model | Prevented diet-induced obesity and insulin resistance | PMID 25738459 |
| 15 mg/kg (≈3×/week, late-life initiated) | Intraperitoneal (IP) | Mouse, aging / exercise-capacity study | Increased physical capacity and improved healthspan measures in older mice | PMID 33473109 |
| ≈10 µM | In vitro (cell culture) | Cell, mechanism (HEK293) | Folate-cycle inhibition → AICAR accumulation → AMPK activation | PMID 25738459 |
11ChemistryMolecular identity
- Molecular weight
- 2174.6 g/mol
- Molecular formula
- C101H152N28O22S2
- Monoisotopic mass
- 2173.11 Da
- Sequence (16 AA)
- MRWQEMGYIFYPRKLR (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg)PubChem CID 146675088; Lee 2015
- Origin
- Mitochondrial-derived peptide (MDP); encoded by a short ORF within the mtDNA 12S rRNA regionLee 2015 (PMID 25738459)
- CAS / UNII
- 1627580-64-6 · A5CV6JFB78 (not independently registry-cross-verified)PubChem CID 146675088; FDA UNII
- Molecular target
- AMPK pathway (via folate/one-carbon cycle / AICAR); nuclear gene regulation under metabolic stressLee 2015 / Kim 2018
- Half-life
- Not established (no validated human pharmacokinetics)Not established
- Regulatory status
- Not approved as a drug anywhereRegulatory record (no approval exists)
12Primary sourcesReferences
- PubChem CID 146675088PubChem CID 146675088 (MOTS-c; C101H152N28O22S2, MW 2174.6, 16-aa sequence MRWQEMGYIFYPRKLR; CAS 1627580-64-6; FDA UNII A5CV6JFB78)
- PMID 25738459Lee et al., Cell Metab 2015 (discovery; 12S-rRNA-encoded MDP; folate→AICAR→AMPK; mouse insulin sensitization, anti-obesity; mouse IP doses)
- PMID 29983246Kim et al., Cell Metab 2018 (MOTS-c translocates to the nucleus to regulate nuclear gene expression under metabolic stress; NRF2/ARE; AMPK-dependent; in vitro)
- PMID 33473109Reynolds et al., Nat Commun 2021 (mouse exercise capacity across ages + healthspan; mouse age-related decline of MOTS-c in muscle/circulation; in humans, exercise induces endogenous MOTS-c in muscle and blood; CohBar COI disclosed)
- PMID 32052315Ikonomidis et al., J Thromb Thrombolysis 2020 (MOTS-c measured as a human biomarker in type-2 diabetes with coronary artery disease; observational)
- NCT04027712Observational study measuring MOTS-c as a biomarker in type-2 diabetes/CAD (MOTS-c not administered)
- PMID 38170165Kumagai et al., Am J Physiol Endocrinol Metab 2024 (MOTS-c limits muscle loss over 8 days of hindlimb immobilization in mice; myostatin and circulating inflammatory cytokines lowered)
- PMID 33554779Kumagai et al., Am J Physiol Endocrinol Metab 2021 (plasma MOTS-c inversely correlated with plasma myostatin in 105 Japanese men; mouse and myotube atrophy work)
- ClinicalTrials.gov NCT03998514Phase 1a/1b trial of CB4211, an analog of MOTS-c, in healthy subjects and subjects with nonalcoholic fatty liver disease (CohBar, Inc.; 88 enrolled; completed April 2021)
- SEC Form 8-K (CohBar, Aug 10, 2021)CohBar, Inc., Phase 1a/1b topline results for CB4211 (SEC Form 8-K press release and presentation, August 10, 2021; ALT and AST changes vs placebo, injection-site reaction rates)
MOTS-c
20 mg vial
Ki Researcher is affiliated with Ki Peptides.
Ships to the US only. Buyers must be 21 or older.
Reviewed by Ki Researcher Team · Research use only · Not medical advice · Updated 2026-10-19