SS-31
Elamipretide (SS-31)
SS-31 (Elamipretide) is a mitochondria-targeting tetrapeptide (D-Arg-2',6'-dimethylTyr-Lys-Phe-NH2) that selectively concentrates in the inner mitochondrial membrane by binding to cardiolipin. It is primarily investigated for conditions involving mitochondrial dysfunction including heart failure, renal ischemia-reperfusion injury, age-related mitochondrial decline, and neurodegenerative diseases. In research settings it is also used for its potential to enhance mitochondrial bioenergetics, reduce oxidative stress, and improve cellular energy production in aging tissues.
Mechanism of Action
SS-31 binds with high affinity to cardiolipin, a phospholipid unique to the inner mitochondrial membrane, stabilizing its interaction with cytochrome c and preserving the electron transport chain architecture essential for ATP synthesis. By preventing cardiolipin peroxidation, it reduces mitochondrial reactive oxygen species (ROS) generation and inhibits the release of pro-apoptotic factors like cytochrome c into the cytoplasm. This cardiolipin-protective action restores mitochondrial membrane potential, improves cristae morphology, and enhances oxidative phosphorylation efficiency without acting as a direct free radical scavenger.
Evidence by Health Goal(16 goals)
Dosing Protocols
Morning, subcutaneous injection into abdomen or thigh
Cycle: 4–8 weeks on, 2–4 weeks off; reassess based on response
Clinical trials have used 0.05–0.25 mg/kg/hr IV infusion for acute indications and subcutaneous dosing of 4–40 mg/day for chronic use. Research-grade self-administration typically uses 5–10 mg/day subcutaneously. Reconstitute lyophilized powder in bacteriostatic water; store reconstituted peptide refrigerated and use within 30 days.
Safety & Side Effects
SS-31 has demonstrated a generally favorable safety profile in Phase I and II human clinical trials, with the majority of adverse events being mild and localized to injection sites. However, it remains an investigational compound with no FDA-approved indication to date, long-term safety data beyond 12 months are limited, and self-administration outside a clinical context carries inherent risks related to sterility, dosing accuracy, and unmonitored systemic effects.
Possible Side Effects
- !Injection site reactions including erythema, induration, and transient pain (most common, ~30–40% in trials)
- !Mild transient nausea reported in a subset of clinical trial participants
- !Headache occurring shortly after administration
- !Fatigue or transient malaise in the initial days of use
- !Dizziness or lightheadedness, possibly related to transient blood pressure changes
- !Hypersensitivity or allergic-type reactions (rare but reported)
- !Elevated liver enzymes (ALT/AST) observed in a small number of trial participants at higher doses
Interactions
- -May potentiate hypotensive effects of antihypertensive medications due to improved cardiac and vascular mitochondrial function — monitor blood pressure closely
- -Theoretical synergy with CoQ10 or MitoQ supplementation; combined use may cause additive mitochondrial membrane effects that are not fully characterized
- -May interact with immunosuppressants in transplant patients given its cardiolipin-stabilizing effects on immune cell mitochondria — use with caution
- -Concurrent use with anticoagulants or antiplatelets warrants monitoring, as mitochondrial improvement in platelets could theoretically alter platelet function
- -Co-administration with nephrotoxic drugs (e.g., NSAIDs, aminoglycosides) may alter renal handling given SS-31's mitochondrial protective effects in renal tubular cells — effect direction uncertain
Cost & Where to Buy
Research-grade SS-31 from reputable peptide vendors typically costs $50–$200 per vial (5–10 mg lyophilized), with monthly costs depending heavily on dose used. A 5 mg/day protocol costs approximately $150–$400/month. Pharmaceutical-grade elamipretide (Stealth BioTherapeutics) is not commercially available for purchase; research-grade purity and sterility vary significantly by vendor.
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