SS-31 (Elamipretide) Protocol Guide
SS-31 (Elamipretide, also known as Bendavia and MTP-131) is a mitochondria-targeted tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2. It selectively concentrates in the inner mitochondrial membrane by binding to cardiolipin, stabilizing cristae architecture, optimizing electron transport chain efficiency, reducing reactive oxygen species, and restoring ATP production. SS-31 has advanced through multiple clinical trials for Barth syndrome, primary mitochondrial myopathy, heart failure, and age-related macular degeneration, receiving FDA Fast Track and Orphan Drug designations.
Protocol Overview
- Compound
- SS-31 (Elamipretide / Bendavia / MTP-131)
- Category
- Mitochondria-Targeted Peptide
- Mechanism
- Binds cardiolipin on inner mitochondrial membrane, stabilizes cristae, optimizes ETC complex interactions, reduces ROS, restores ATP synthesis
- Sequence
- D-Arg-Dmt-Lys-Phe-NH2 (4 amino acids, cell-permeable)
- Half-Life
- ~4 hours (subcutaneous)
- Vial Size
- 40mg lyophilized powder (typical)
- Route
- Subcutaneous injection
- Frequency
- Once daily
- Cycle Length
- 4-12 weeks
Dosing Protocol
| Protocol | Dose | Frequency | Route | Duration |
|---|---|---|---|---|
| Conservative | 20 mg | Once daily | Subcutaneous | 4-8 weeks |
| Standard (Clinical) | 40 mg | Once daily | Subcutaneous | 8-12 weeks |
| Weight-Based | 0.25 mg/kg | Once daily | Subcutaneous | 4-12 weeks |
| Acute (IV Research) | 0.05 mg/kg/hr | Continuous infusion | Intravenous | Single session |
Note: The 40mg daily subcutaneous dose is the most studied in clinical trials (TAZPOWER, ReCLAIM, MMPOWER). Weight-based dosing at 0.25 mg/kg is an alternative approach for individualized protocols.
Reconstitution Instructions
Materials Needed
- SS-31 40mg lyophilized vial
- Bacteriostatic water (2mL)
- 3mL mixing syringe (18-20ga)
- Insulin syringes (29-31ga) for dosing
- Alcohol swabs
Reconstitution Steps
- Clean vial stopper with alcohol
- Draw 2mL bacteriostatic water
- Inject slowly down the vial wall
- Gently swirl (never shake)
- Wait 5 minutes for full dissolution
- Concentration: 20 mg/mL
| Dose | Volume (2mL recon) | Insulin Syringe |
|---|---|---|
| 10 mg | 0.50 mL | 50 units |
| 20 mg | 1.00 mL | 100 units (full syringe) |
| 40 mg | 2.00 mL | Full vial (use 1mL syringe x2) |
Administration Guide
Injection Sites
- Primary: Abdomen (2 inches from navel)
- Alternate: Anterior thigh (outer quadrant)
- Alternate: Upper arm (deltoid region)
- Rotate injection sites daily
- Avoid areas with bruising or scarring
Timing & Storage
- Timing: Morning administration preferred
- With food: Can be administered regardless of meals
- Storage (lyophilized): Room temperature or refrigerate
- Storage (reconstituted): Refrigerate 2-8°C, use within 28 days
- Do not freeze reconstituted solution
Expected Timeline
Side Effects & Monitoring
Common Side Effects
- Injection site reactions (redness, swelling, pain) - most common
- Headache (mild, transient)
- Nausea (uncommon)
- Fatigue (paradoxical, usually resolves)
SS-31 has demonstrated a favorable safety profile in Phase II/III clinical trials with most adverse events being mild injection site reactions.
Precautions
- Monitor renal function (eGFR) at baseline and periodically
- Clinical trial exclusions include severe hepatic impairment
- Not recommended during pregnancy or breastfeeding
- May interact with other mitochondrial-targeted compounds
Stacking Recommendations
Compatible Compounds
- NAD+ precursors (NMN/NR): Complementary mitochondrial support via different pathways
- MOTS-c: Mitochondrial-derived peptide for metabolic optimization
- CoQ10: Electron transport chain cofactor support
- Humanin: Another mitochondrial-derived peptide for cytoprotection
- PQQ: Mitochondrial biogenesis support
Popular Stacks
- Mito Optimization: SS-31 40mg/day + NAD+ + CoQ10
- Longevity Stack: SS-31 + MOTS-c + Humanin
- Energy Recovery: SS-31 + PQQ + Alpha-lipoic acid
Blood Work Recommendations
| Panel | Markers | Timing |
|---|---|---|
| Basic Panel | CBC, CMP | Baseline, Week 6, Week 12 |
| Mitochondrial | Lactate, pyruvate, CoQ10 levels | Baseline, Week 6 |
| Oxidative Stress | 8-OHdG, F2-isoprostanes, MDA | Baseline, Week 6 |
| Cardiac (if applicable) | NT-proBNP, troponin, BNP | Baseline, Week 6, Week 12 |
| Renal Function | eGFR, BUN, creatinine | Baseline, Week 4, Week 8 |
Mitochondrial biomarkers (lactate/pyruvate ratio) provide the most relevant tracking data for SS-31 protocols. Oxidative stress markers help quantify ROS reduction.
Related Tools & Resources
