LA LABResearch Reference Document
Compound Guide
MOTS-c — Mitochondrial-Derived Peptide
Quick Start
What It Is
MOTS-c is a 16-amino acid peptide encoded by the mitochondrial genome (12S rRNA region) — the first mitochondrial-encoded peptide shown to have systemic endocrine effects. It is naturally secreted from mitochondria in response to stress (exercise, heat, caloric restriction) and acts as a metabolic regulator, signalling through AMPK pathways in skeletal muscle and adipose tissue.
Research Dosing
5 mg SubQ, 2–3× per week. Inject slowly — histamine response (flushing, warmth) is common during rapid injection. Slow injection over 30–60 seconds significantly reduces this response. Half-life is short; the mechanism works through downstream AMPK signalling rather than sustained plasma levels.
Regulatory & Doping Status
Not FDA-approved. Removed from Category 2 effective April 22, 2026; PCAC review July 23, 2026. WADA banned under S4.4.1 (Metabolic modulators — AMPK activators) — same class as AICAR. For competitive athletes, MOTS-c is prohibited. For research purposes only.
Dosing Protocol
| Protocol | Dose | Frequency | Duration | Notes |
|---|---|---|---|---|
| Standard | 5 mg | 2–3× per week | 4–8 weeks | Inject slowly to minimise histamine response |
| Conservative | 2.5–5 mg | 2× per week | 4 weeks | Starting dose; assess histamine tolerance |
| Wash-out | — | — | 4 weeks minimum | Allow off-cycle before resuming |
Histamine Response — Inject Slowly
Flushing and localised warmth at the injection site are common with MOTS-c, particularly with rapid injection. This is a histamine-mediated response, not an allergic reaction. Injecting over 30–60 seconds (rather than rapidly) substantially reduces the response. Pre-dosing with antihistamine can also attenuate this effect in research protocols.
Supplies & Reconstitution
Reconstitution Math — 10 mg Vial (3 mL BAC)
| Target Dose | Units (U-100) | Doses / Vial |
|---|---|---|
| 2.5 mg | 75.0 units | 4 |
| 5 mg | 150.0 units | 2 |
| 10 mg | 300.0 units | 1 |
Reconstitute the 10 mg vial with 3.0 mL bacteriostatic water → 3.33 mg/mL. U-100 syringe = 100 units per mL. Swirl gently — do not shake. Refrigerate 2–8°C.
Reconstitution Steps
01
Warm the vial
Allow lyophilised vial to reach room temperature from freezer.
02
Swab and draw
Alcohol swab both vial tops, air-dry. Draw required BAC water volume.
03
Inject along the wall
Run BAC water slowly down the inside glass wall. Do not jet onto the powder.
04
Swirl gently
Swirl until clear. Do not shake or vortex.
05
Refrigerate and inject slowly
Store at 2–8°C for up to 30 days. When injecting, depress the plunger slowly over 30–60 seconds to minimise histamine response. Protect from light.
Mechanism of Action
AMPK Activation
Primary proposed mechanism: activates AMP-activated protein kinase (AMPK) in skeletal muscle and other metabolic tissues. AMPK is the master metabolic switch activated by caloric deficit, exercise, and metformin — it shifts cells toward fat oxidation and glucose uptake.
Glucose Uptake
AMPK activation stimulates GLUT4 translocation to the plasma membrane in muscle cells, increasing non-insulin-dependent glucose uptake. Studied in insulin resistance and metabolic syndrome models in mice and cell culture.
Fat Oxidation
AMPK inhibits ACC (acetyl-CoA carboxylase), reducing malonyl-CoA and allowing carnitine palmitoyltransferase 1 (CPT1) to transport fatty acids into the mitochondria for beta-oxidation. Net effect: increased fat burning.
Mitochondrial Biogenesis
Downstream AMPK → PGC-1α signalling promotes mitochondrial biogenesis (synthesis of new mitochondria) and upregulates NRF2 / antioxidant defences. Studied in models of age-related metabolic decline.
Research Status
No Human RCT for Native MOTS-c
As of mid-2026, no published human RCT exists for native MOTS-c. CB4211, a synthetic analogue, completed Phase 1 (safe and tolerated in humans), but this is not the same compound. The extensive preclinical data is from mouse models and in vitro studies. The relevance to human biology is promising but not yet confirmed by human trials.
| Study Type | Finding |
|---|---|
| Lee et al. 2015 (Nature Medicine) | Discovery of MOTS-c; AMPK activation; improved insulin sensitivity in mice |
| Exercise physiology studies | Endogenous MOTS-c levels rise during exercise; positively correlate with VO2max |
| CB4211 Phase 1 (analogue) | Safe and well tolerated; metabolic endpoints exploratory at Phase 1 stage |
| Ageing studies (mice) | Extended healthspan in old mice; improved motor function and metabolic parameters |
Storage
| State | Temperature | Duration | Notes |
|---|---|---|---|
| Lyophilised (powder) | −20°C (freezer) | Up to 24 months | Protect from light and moisture |
| Reconstituted (liquid) | 2–8°C (refrigerator) | Up to 30 days | Do not freeze after reconstitution; protect from light |
Disclaimer
This document is an educational research reference only. MOTS-c is not FDA-approved and is WADA banned (S4.4.1) for competitive athletes. No human RCT exists for native MOTS-c. By purchasing from LA LAB you confirm you are 18+ and that products are for research purposes only.