SS-31
Dosage Protocol
SS-31 (Elamipretide; D-Arg-Dmt-Lys-Phe-NH₂) is a mitochondria-targeted tetrapeptide developed by Hazel Shen Szeto and Peter Schiller. It selectively concentrates in the inner mitochondrial membrane, binds cardiolipin, prevents cytochrome c peroxidase activity, and reduces reactive oxygen species — restoring mitochondrial structure and function in aging and disease models.
What is SS-31?
SS-31 belongs to the Szeto-Schiller family of aromatic-cationic tetrapeptides that selectively partition into the inner mitochondrial membrane (IMM) at 1000-fold concentration relative to cytoplasm, driven by the large negative membrane potential (ΔΨm). Its alternating aromatic-cationic structure allows it to interact specifically with cardiolipin — a phospholipid unique to the IMM that is critical for cristae architecture and electron transport complex assembly.
By stabilizing cardiolipin, SS-31 preserves mitochondrial cristae structure, restores electron transport chain (ETC) efficiency, reduces superoxide production, and prevents cytochrome c from acting as a peroxidase. The compound has demonstrated efficacy in cardiac ischemia-reperfusion, chronic kidney disease, skeletal muscle aging, and neurodegenerative disease models.
Dosing Schedule
Parameters documented in published preclinical and clinical research.
| Phase | Dose | Frequency | Duration | Notes |
|---|---|---|---|---|
| Conservative | 500 mcg SubQ | Once daily | Weeks 1–2 | Start here. Titrate up over 2 weeks. Do not start at 100 mcg — below validated research range. |
| Working dose | 1–5 mg | Once daily | Weeks 2–12 | SubQ. Some protocols use 5 days on / 2 days off. Minimum 8 weeks for meaningful mitochondrial outcomes. |
| Clinical protocol | 40 mg IV infusion | Single dose or daily | Acute protocols | EMBRACE-HF and BETTER trials used IV delivery over 4 hours. Not applicable to SubQ self-administration. |
| Off cycle | — | — | 4–8 weeks | Limited human data — periodic cycling advisable. |
Safety & Side Effects
Academic References
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[1]
Szeto HH. (2014). First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 171(8):2029–50. PubMed ↗
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[2]
Dai DF, et al. (2013). Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondria-targeted peptides. Circ Heart Fail. 6(5):1067–76. PubMed ↗
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[3]
Campbell MD, et al. (2019). Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med. 134:268–81. PubMed ↗
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[4]
Chatfield KC, et al. (2019). Elamipretide improves mitochondrial function in the failing human heart. JACC Basic Transl Sci. 4(2):147–57. PubMed ↗