At a Glance

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino acid mitochondrial-derived peptide that activates the AMPK pathway to improve glucose utilisation, lipid metabolism, and cellular energy homeostasis.[1] It functions as an exercise mimetic and metabolic regulator, with emerging research into longevity and insulin sensitisation.

Reconstitute: Add 3.0 mL bacteriostatic water → 3.33 mg/mL concentration.
Dose range: 200–1,000 mcg/day subcutaneously, gradually increasing over 10+ weeks.
Easy measuring: At 3.33 mg/mL on a U-100 syringe, 1 unit = 0.01 mL = 33.3 mcg. A 500 mcg dose = 15 units / 0.15 mL.
Storage: Lyophilised: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C; use within 7 days for optimal potency.

Overview

Goal: Activate AMPK-driven metabolic pathways to improve glucose utilisation, mitochondrial biogenesis, and exercise capacity.[1]
Schedule: Daily subcutaneous injection for 10+ weeks with gradual dose escalation.
Dose range: 200–1,000 mcg per injection.
Reconstitution: 3.0 mL BAC water per 10 mg vial → 3.33 mg/mL.
Injection site: Abdomen, outer thighs, or upper arms (rotate systematically).

What You’ll Need

Plan based on a 10-week gradual cycle (200 mcg/day for 4 weeks, then 500 mcg/day for 6 weeks — 70 injections, 24.6 mg total).

MOTS-c Vials (10 mg each): 24.6 mg needed ÷ 10 mg per vial → 3 vials.
Insulin Syringes (U-100, 1 mL): 70 injections → 70 syringes.
Bacteriostatic Water (10 mL bottles): 3.0 mL per vial → 1 × 10 mL bottle.
Alcohol Swabs: 2 per injection → 140 swabs per 10-week cycle.

How to Reconstitute

Allow frozen lyophilised vial to reach room temperature (10–15 minutes).
Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the inner vial wall to avoid foaming.
Gently swirl until fully dissolved — do not shake vigorously. Solution should be clear.
Label with reconstitution date; refrigerate at 2–8 °C. Use within 7 days for optimal potency.

Dosing Schedule

Water: 3.0 mL → Concentration: 3.33 mg/mL → 1 unit = 33.3 mcg

Week	Daily Dose	Units (U-100)	Volume	Frequency
1–2	200 mcg	6 units	0.06 mL	Once daily
3–4	400 mcg	12 units	0.12 mL	Once daily
5–6	600 mcg	18 units	0.18 mL	Once daily
7–8	800 mcg	24 units	0.24 mL	Once daily
9–10+	1,000 mcg	30 units	0.30 mL	Once daily

Begin at 200 mcg daily and titrate up every 2 weeks as tolerated. MOTS-c has a short plasma half-life, but triggers sustained AMPK/NRF2 transcriptional cascades lasting well beyond clearance.[1]

Protocol Details

Weeks 1–4: 200 mcg daily (6 units / 0.06 mL) — tolerability assessment.
Weeks 5–8: 500 mcg daily (15 units / 0.15 mL) — moderate dose.
Weeks 9+: 1,000 mcg daily (30 units / 0.30 mL) — full dose.
Cycle: 10–12+ weeks on; 4-week break before repeating.

Storage

Lyophilised: Store at −20 °C (−4 °F); protect from moisture and light.
Reconstituted: Refrigerate at 2–8 °C. Use within 7 days (shorter than most peptides). Do not freeze.
Appearance: Clear solution. Discard if cloudy, coloured, or particulate.

How MOTS-c Works

MOTS-c is a 16-amino acid peptide encoded in the mitochondrial genome (12S rRNA gene). Unlike nuclear-encoded peptides, MOTS-c is produced directly by mitochondria and acts as a retrograde signal from mitochondria to the nucleus, regulating metabolic gene expression.[1]

Its primary mechanism involves activation of AMP-activated protein kinase (AMPK), the master metabolic switch that enhances glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. MOTS-c also activates the NRF2 antioxidant pathway, supporting cellular stress resistance and longevity-associated gene expression. Exercise naturally elevates MOTS-c levels, which is why it is often described as an “exercise mimetic” peptide.[2]

Good to Know

MOTS-c has a very short reconstituted shelf life (7 days) compared to most peptides — plan your injection schedule accordingly to minimise waste.
WADA-prohibited substance — competitive athletes subject to anti-doping rules must not use MOTS-c.
Best administered in the morning or pre-exercise to align with natural metabolic rhythms.
Despite the short plasma half-life (~30 minutes), MOTS-c triggers sustained AMPK and NRF2 signalling cascades that persist for hours.
Ensure ≥99% purity; research-grade peptides with lower purity may contain toxic impurities.
Metabolic improvement: Activates AMPK to improve glucose utilisation and insulin sensitivity in preclinical models.[1]
Exercise mimetic: Replicates some molecular benefits of exercise, including enhanced mitochondrial biogenesis and improved endurance capacity.
Longevity research: MOTS-c levels decline with age; supplementation may counteract age-related metabolic decline.[2]
Side effects: Reported effects include increased heart rate, injection site irritation, occasional insomnia, headache, and mild GI symptoms — generally mild and transient.
Regulatory status: Not FDA-approved; WADA-prohibited. No completed clinical trials establishing definitive safety or efficacy.
For background on MOTS-c's mechanism, evidence, and safety profile, see What Is MOTS-c?.

Tips for Best Results

Pair with regular exercise (both aerobic and resistance training) to complement AMPK activation.
Maintain a balanced diet with adequate complex carbohydrates to support enhanced glucose metabolism.
Prioritise sleep (7–9 hours) — mitochondrial biogenesis is enhanced during restorative sleep phases.
Stay well hydrated, especially if combining MOTS-c with fasted training.

Injection Tips

Clean the vial stopper and injection site with separate alcohol swabs; allow both to air-dry fully before proceeding.
Using a 29–31 gauge insulin syringe (5/16″ to 1/2″ needle), draw the calculated dose precisely.
Pinch a fold of skin and insert the needle at 45° into subcutaneous fat (90° is acceptable with a short needle into a well-pinched fold).
Inject slowly over 2–3 seconds; do not aspirate. Withdraw the needle, apply gentle pressure, and do not rub the site.
Rotate injection sites (abdomen, thighs, upper arms) and dispose of each syringe in a sharps container immediately after use.

MOTS-c (10 mg)