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Reviewed by MyPeptideMatch Editorial TeamLast reviewed February 2026Updated February 2026

SS-31 (Elamipretide) Dosing Protocol: 10 mg Vial — Mitochondrial Protection Guide

SS-31 (elamipretide) tetrapeptide dosing guide for the 10 mg vial — mitochondrial membrane potential restoration for aging, heart failure, and metabolic disease.

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Quickstart highlights

SS-31 (D-Arg-Dmt-Lys-Phe-NH2, elamipretide) is a 4-amino acid cell-permeable mitochondria-targeting tetrapeptide developed by Hazel Szeto and Peter Schiller at Cornell.

  • Concentration: 2 mg/mL (10 mg vial + 5 mL bacteriostatic water).
  • At 2 mg/mL: 4 mg/day = 200 units (2 mL); divide into two 1 mL SC injections for comfort.
  • PROGRESS trial: SS-31 40 mg/day x 5 days significantly improved LV function and 6MWT in HFpEF.
  • Inject in the morning; SS-31 concentrates in mitochondrial inner membranes within 1 hour of injection.
  • Store lyophilized form at -20 °C; reconstituted at 2–8 °C, use within 14 days.

Dosing table

For educational reference only. Your prescribing provider may adjust doses based on your clinical profile and response.

WeekDose (µg)UnitsFrequencyNotes
1-22000100Once daily (morning)2 mg — 100 units; starting dose; assess tolerance before advancing
3-124000200Once daily (morning)4 mg — 200 units (2 mL); standard dose from human clinical trials; 10 mg vial provides 2.5 doses at this level

Reconstitution steps

  1. Draw 5 mL bacteriostatic water (two 2.5 mL draws); inject slowly down the vial wall.
  2. Swirl gently until dissolved; do not shake.
  3. Final concentration: 2 mg/mL. At 2 mg/mL: 2 mg = 100 units, 4 mg = 200 units (2 mL draw).
  4. Label with date; refrigerate at 2–8 °C. Use within 28 days.

Supplies needed

12-week plan

  • 6 vials
  • 84 syringes
  • 30 mL bac water
  • 84 alcohol swabs
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Protocol overview & cycle notes

Restore mitochondrial membrane potential, reduce reactive oxygen species production, and improve cellular energy metabolism through daily SS-31 subcutaneous injections targeting cardiolipin-inner membrane architecture.

Cycle length: 12 weeks on.

Off-cycle: 8 weeks off; reassess mitochondrial function biomarkers (lactate:pyruvate ratio, 6MWT) before resuming.

Storage & handling

Lyophilized: store at -20 °C (SS-31 is more sensitive to temperature than most peptides). Reconstituted at 2 mg/mL: refrigerate 2–8 °C; use within 14 days (more conservative than typical peptides due to SS-31's charge-sensitive stability). Protect from light.

Injection & tracking tips

  • Inject subcutaneously in the morning — SS-31 bioavailability peaks within 1 hour and correlates with mitochondrial ATP production enhancement.
  • For the 4 mg dose, the injection volume is 2 mL — divide into two 1 mL subcutaneous injections at adjacent sites for comfort.
  • SS-31 has high positive charge (net +3) and binds cardiolipin on mitochondrial inner membranes; systemic SC injection distributes to all tissues.

Tracking

Logging helps you and your provider spot patterns and adjust dose or timing.

  • Measure 6-minute walk test (6MWT) distance at baseline and every 4 weeks for functional capacity assessment.
  • Track fatigue on a validated scale (FSS — Fatigue Severity Scale) weekly.
  • Monitor fasting lactate:pyruvate ratio at baseline and end of protocol as mitochondrial function proxy.
Log your cycle in the calculator →

How this works & references

SS-31 (D-Arg-Dmt-Lys-Phe-NH2, elamipretide) is a 4-amino acid cell-permeable mitochondria-targeting tetrapeptide developed by Hazel Szeto and Peter Schiller at Cornell. The alternating cationic-aromatic structure enables concentration in mitochondrial inner membranes through electrostatic interaction with cardiolipin (an anionic phospholipid unique to the inner membrane). SS-31 (1) stabilizes cardiolipin-cytochrome c interaction, preserving electron transport chain efficiency; (2) scavenges mitochondrial ROS directly at the production site; (3) restores mitochondrial cristae morphology. In the PROGRESS Phase 2 trial (NCT02388464, n=36), SS-31 (elamipretide) 40 mg/day subcutaneous for 5 days significantly improved left ventricular end-systolic volume and 6MWT distance in heart failure with preserved ejection fraction.

Sources

  • Source: Szeto HH — First-in-class cardioprotective agent SS-31 targeting mitochondrial cardiolipin. Future Med Chem. 2015;7(2):201-16
  • Source: Daubert MA et al. — Elamipretide (SS-31) in HFpEF: PROGRESS trial. JACC Heart Fail. 2017;5(9):631-643

Frequently asked questions

What conditions is SS-31 being studied for?
SS-31 (elamipretide) is in clinical development for: (1) Heart failure with preserved ejection fraction (HFpEF — PROGRESS trial); (2) Barth syndrome (mitochondrial cardiomyopathy — FDA Rare Pediatric Disease designation); (3) Leber hereditary optic neuropathy (LHON); (4) Primary mitochondrial myopathy. Off-label use includes sarcopenia, mitochondrial aging, and metabolic dysfunction.
How does SS-31 differ from other mitochondria-targeting antioxidants (MitoQ, SkQ1)?
MitoQ and SkQ1 are lipophilic cation-based small molecules that concentrate in the mitochondrial matrix via membrane potential gradient. SS-31 concentrates specifically in the inner membrane via cardiolipin binding — different from the matrix. SS-31 does not require high membrane potential for accumulation (important in damaged mitochondria) and directly stabilizes cristae structure rather than just quenching ROS.
Why should SS-31 be stored at -20 °C instead of room temperature?
SS-31 contains the unusual amino acid 2',6'-dimethyltyrosine (Dmt) and a C-terminal amide. The positive charge at three positions makes it susceptible to chemical degradation (beta-elimination, deamidation) at temperatures above 2–8 °C when in solution. Lyophilized SS-31 is more stable but benefits from -20 °C frozen storage for long-term preservation. Reconstituted solution is less stable than most peptides — use within 14 days.
What dose did the human clinical trials use?
The PROGRESS HFpEF trial used 40 mg/day subcutaneous for 5 consecutive days. The compounding use dose of 4 mg/day reflects a more conservative maintenance approach — the 40 mg/day clinical dose was for intensive short-course intervention in cardiac disease patients. For healthy aging and metabolic optimization, 2–4 mg/day for extended periods is the common off-label approach.
Can SS-31 improve exercise performance in healthy individuals?
Theoretically yes — mitochondrial efficiency enhancement (ATP production per unit oxygen consumed) is the proposed mechanism for improved fatigue resistance and physical performance. Szeto et al. animal data shows improved treadmill performance in aged mice at SS-31 doses equivalent to ~2 mg/day in humans. No published RCT in healthy exercising humans exists as of 2026.

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This content is for informational purposes only and does not constitute medical advice. Consult a licensed healthcare provider before starting any peptide therapy. Dosing and protocols may vary by formulation and prescriber.

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