MOTS-c Dosage Guide: Protocols, Timing & Results (2026)

Dose: 5 mg subcutaneously, once per week. Duration: 8 to 12 weeks. This is the starting point for first-time users.

Inject the full 5 mg in a single session. Run this protocol for at least two weeks to gauge tolerance before considering an increase. Most users settle here and report meaningful results by week four.

The beginner dose is sufficient for metabolic improvement and body composition changes. More is not always better with MOTS-c. Research on the MOTS-c analog CB4211 used 25 mg per day (a much higher dose), but native MOTS-c protocols trend lower.

Dose: 10 mg per week, split into two 5 mg injections (e.g., Monday and Thursday). Duration: 8 to 12 weeks.

This protocol targets athletes and body recomposition goals. Splitting the dose maintains more consistent AMPK activation across the week. Inject 30 to 60 minutes before exercise when possible for synergy with training-induced AMPK signaling.

The performance protocol costs twice the beginner protocol. Use the Peptide Cost Calculator to estimate total cycle expense before committing.

Dose: 5 mg once weekly. Duration: 8 to 12 weeks, repeated 2 to 3 times per year.

This is the conservative approach for general metabolic health and longevity. Once-weekly dosing provides baseline AMPK activation and mitochondrial support without chronic pathway stimulation. Cycle on and off to avoid AMPK pathway tolerance.

Pairs well with Epitalon for a multi-pathway anti-aging approach. MOTS-c addresses mitochondrial decline; Epitalon targets telomere maintenance. Two distinct hallmarks of aging, covered by two peptides.

The same protocols apply. Performance protocol (10 mg/week) produces faster body composition changes. The beginner protocol (5 mg/week) works for users combining MOTS-c with structured diet and training.

MOTS-c promotes fat oxidation through AMPK-mediated lipolysis and targets visceral fat specifically. It preserves lean muscle mass during caloric restriction, a meaningful advantage over GLP-1 agonists like semaglutide.

A Reddit user documented dropping from 18% to 15% body fat in 15 days on MOTS-c. Typical results are more gradual. Expect visible body composition shifts at the 6 to 8 week mark.

Women use the same dosage ranges as men. No sex-specific dose adjustments are established in the research.

Start with the beginner protocol (5 mg/week) and assess for two weeks. Women report similar results timelines and side effect profiles as men. The 10 mg/week performance protocol is appropriate for women pursuing body recomposition or athletic performance goals.

Standard approach: add 2 mL of bacteriostatic water to a 10 mg vial. This produces a concentration of 5 mg/mL.

1. 1.Bring both the vial and bacteriostatic water to room temperature.
2. 2.Wipe the rubber stopper on the vial and the BAC water vial with an alcohol swab.
3. 3.Draw 2 mL of bacteriostatic water with an insulin syringe.
4. 4.Insert the needle into the MOTS-c vial at an angle and let the water trickle slowly down the glass wall. Do not squirt directly onto the powder.
5. 5.Do not shake. Let the water dissolve the powder naturally, or swirl the vial gently.
6. 6.Once fully dissolved, the solution should be clear.

For finer dose control, add 3 mL instead of 2 mL, producing a 3.33 mg/mL concentration. Use the Peptide Reconstitution Calculator to compute exact volumes for any vial size.

Route: subcutaneous injection. This is a shallow injection into the fat layer beneath the skin.

Use an insulin syringe (29 to 31 gauge, 0.5 mL or 1 mL). Preferred injection sites: abdomen (2 inches from the navel), outer thigh, or upper arm. Pinch the skin, insert the needle at a 45-degree angle, inject slowly, wait a few seconds, then withdraw.

Rotate injection sites with each dose. This prevents localized irritation and scar tissue formation. For a full visual walkthrough, see the peptide injection guide.

Lyophilized (unreconstituted): store at minus 20 degrees Celsius in a freezer. Stable for months.

Reconstituted: refrigerate at 2 to 8 degrees Celsius. Use within 14 to 30 days. Do not freeze reconstituted solution. Avoid repeated freeze-thaw cycles.

Protect from direct light. Keep the vial upright. If the solution becomes cloudy or discolored after reconstitution, discard it.

For a general reconstitution walkthrough covering all peptides, see How to Reconstitute Peptides. For injection technique, site rotation, and needle selection, see the Peptide Injection Guide.

Subtle energy increase during the day. Improved workout recovery. Some users report mild fatigue as the body adjusts to altered metabolic signaling.

Do not expect visible changes yet. Cellular adaptation is underway: AMPK activation is ramping up, glucose uptake is improving, and mitochondrial biogenesis is beginning.

Noticeable energy improvement. Fasting glucose may start trending downward. The initial metabolic shift becomes perceptible.

Users with metabolic syndrome or insulin resistance often see the earliest improvements. Improved carbohydrate tolerance and reduced post-meal energy crashes are commonly reported.

Improved stamina and endurance during exercise. Reduced systemic inflammation. Body composition changes begin.

This is the inflection point. Mitochondrial density has increased enough to produce measurable performance differences. In the Reynolds et al. mouse study, old mice treated with MOTS-c doubled their running capacity on treadmill tests.

Fat loss becomes visible, particularly around the midsection. Visceral fat reduction improves waist-to-hip ratio. Strength gains from better energy production.

This is where MOTS-c separates from placebo in most user reports. Training capacity is higher, recovery is faster, and the mirror starts confirming what the scale has been showing.

Peak body recomposition. Sustained energy throughout the day. Metabolic markers (fasting glucose, insulin sensitivity, lipid profile) at their best.

This is the end of a standard cycle. Some users extend to 12 weeks; others stop at 8. Benefits gradually fade over 4 to 8 weeks after discontinuation without continued dosing.

AMPK activation is the headline mechanism. When AMPK fires, cells shift from energy storage to energy burning. Glucose uptake increases through GLUT4 translocation. Fat oxidation ramps up. Mitochondrial biogenesis accelerates.

In the foundational mouse study, MOTS-c prevented diet-induced obesity and reversed insulin resistance without changes in food intake or exercise (Lee et al. 2015, Cell Metabolism). The beginner protocol (5 mg/week) is sufficient for metabolic improvement.

MOTS-c promotes fat oxidation through AMPK-mediated lipolysis. It targets visceral fat, the metabolically dangerous fat around organs, preferentially.

Critically, MOTS-c preserves lean muscle mass during fat loss. This distinguishes it from GLP-1 agonists like semaglutide, which produce greater weight loss but carry a risk of muscle wasting. For body recomposition, the performance protocol (10 mg/week) accelerates results.

MOTS-c improves mitochondrial density and cellular energy production. More mitochondria per cell translates to greater oxidative capacity and reduced fatigue.

The 2021 Nature Communications study demonstrated that aged mice (22 months old) treated with MOTS-c doubled their running capacity and outperformed untreated middle-aged mice (Reynolds et al. 2021). Exercise itself induces MOTS-c production in human skeletal muscle. Exogenous dosing compounds that effect.

Mitochondrial dysfunction is a hallmark of aging. Endogenous MOTS-c levels decline as we age. Restoring those levels may reverse aspects of metabolic aging.

Aged mice treated with MOTS-c regained physical performance metrics closer to young mice. The peptide activates antioxidant response elements (ARE genes) in the nucleus, adding a protective layer against oxidative damage. The maintenance protocol (5 mg/week, cycled) is appropriate for longevity-focused use.

Injection site redness or mild swelling. Temporary increase in body temperature from heightened metabolic activity. Mild fatigue during the first week as the body adjusts to altered metabolic signaling. Occasional nausea. Headache.

These effects typically resolve within the first week. Reducing the dose or slowing the injection can help.

Heart palpitations (reported by USADA in their MOTS-c overview). Blood sugar fluctuations, particularly in users who inject while fasting. Flushing. Muscle cramping (rare). Insomnia (rare).

If blood sugar symptoms occur (lightheadedness, shakiness), eat a small meal before or immediately after injection. Reduce the dose if symptoms persist.

Diabetes patients on insulin or sulfonylureas face increased hypoglycemia risk. MOTS-c improves insulin sensitivity, which compounds the glucose-lowering effect of these medications. Monitor blood sugar closely and adjust medication with your physician.

Metformin users should start at a lower dose. Both MOTS-c and metformin activate AMPK through different upstream mechanisms. The combined effect can be stronger than anticipated.

Pregnant or breastfeeding women should not use MOTS-c. People with mitochondrial diseases should consult a specialist before using any compound that alters mitochondrial function. No long-term human safety data exists.

Yes. MOTS-c is prohibited by WADA under category S4: Hormone and Metabolic Modulators. It is banned at all times, in-competition and out-of-competition (WADA 2026 Prohibited List).

Some sources incorrectly classify MOTS-c under S2 (Peptide Hormones). The correct category is S4. Athletes subject to anti-doping testing must not use MOTS-c.

MOTS-c 5 mg twice per week (subcutaneous) plus 5-Amino-1MQ 50 to 100 mg per day (oral). Duration: 8 to 12 weeks.

Why this works: MOTS-c activates AMPK and improves mitochondrial function. 5-Amino-1MQ inhibits NNMT, preventing fat cells from resisting metabolic activation. They target different metabolic bottlenecks. The combination addresses fat metabolism from two directions.

MOTS-c 5 mg once or twice per week for 8 to 12 weeks. Epitalon 5 mg per day for 10 to 20 days (as a short cycle within the MOTS-c cycle).

Why this works: MOTS-c restores youthful metabolic function through mitochondrial biogenesis. Epitalon activates telomerase, the enzyme that maintains telomere length. Two major hallmarks of aging addressed by two peptides operating through completely independent pathways.

MOTS-c 5 mg twice per week plus Ipamorelin 200 to 300 mcg before bed. Duration: 8 to 12 weeks.

Why this works: MOTS-c handles the metabolic and fat-burning side. Ipamorelin's growth hormone release supports muscle growth, recovery, and sleep quality. One peptide burns fat; the other builds tissue.

MOTS-c 5 mg twice per week plus AOD-9604 300 mcg per day plus Tesamorelin 1 to 2 mg per day. Duration: 8 to 12 weeks.

Three distinct mechanisms: AMPK activation (MOTS-c), beta-3 adrenergic lipolysis (AOD-9604), and GHRH-stimulated growth hormone release (Tesamorelin). This is the most aggressive fat-loss stack. Physician supervision is appropriate given the multiple active compounds. Use the Peptide Interaction Checker before combining.

Dr. Changhan David Lee and Pinchas Cohen at the USC Leonard Davis School of Gerontology published the first description of MOTS-c in 2015. It was the first peptide shown to be encoded by mitochondrial DNA that acts as a systemic hormone.

Mice treated with MOTS-c prevented diet-induced obesity and reversed insulin resistance. Fat accumulation decreased without changes in food intake or physical activity. The paper established MOTS-c as an "exercise mimetic" and launched the field of mitochondrial-derived peptide research (Lee C et al., Cell Metab. 2015;21(3):443-454).

This study asked whether MOTS-c could restore physical performance in aged mice. The answer: yes, dramatically.

Aged mice (22 months, equivalent to roughly 65 to 70 human years) treated with MOTS-c three times per week doubled their running capacity on treadmill tests. They outperformed untreated middle-aged mice. The study also confirmed that exercise induces endogenous MOTS-c production in human skeletal muscle, establishing a bidirectional relationship between MOTS-c and physical activity (Reynolds JC et al., Nat Commun. 2021;12(1):470).

CB4211, a MOTS-c analog developed by CohBar, completed Phase 1a/1b clinical trials. This remains the only human clinical data for a MOTS-c-based compound.

Phase 1a: 65 healthy adults received CB4211 with no serious adverse events. Phase 1b: 20 obese patients with NAFLD (non-alcoholic fatty liver disease) received 25 mg per day subcutaneously for 4 weeks. Results versus placebo: ALT decreased 25%, AST decreased 17%, fasting glucose decreased 6%. All differences were statistically significant (CohBar press release, Aug 2021).

CB4211 is an analog, not native MOTS-c. The dosing (25 mg/day) is substantially higher than community MOTS-c protocols (5 to 10 mg/week). These results are directional, not directly translatable.

Zheng et al. published a comprehensive therapeutic review of MOTS-c in Frontiers in Endocrinology (2023), cataloging its effects on metabolism, aging, inflammation, and cardiovascular function (PMC).

A 2025 Frontiers in Physiology study demonstrated that MOTS-c restores mitochondrial respiration in type 2 diabetic hearts. A separate 2025 study showed MOTS-c prevents pancreatic islet cell senescence. The research pipeline continues to expand.