SS-31 (Elamipretide) — Research, Dosing & Price Guide

SS-31 (Elamipretide, Bendavia, MTP-131) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane and restores bioenergetic function. It binds to cardiolipin, a phospholipid unique to mitochondria that is essential for electron transport chain efficiency. SS-31 represents a first-in-class approach to treating mitochondrial dysfunction, with clinical trials in heart failure, Barth syndrome, and age-related mitochondrial decline.

SS-31 (D-Arg-Dmt-Lys-Phe-NH2) is a cell-permeable tetrapeptide with an alternating aromatic-cationic motif that allows it to cross membranes and concentrate >1000-fold in the inner mitochondrial membrane within minutes of administration. Its primary target is cardiolipin, an anionic phospholipid exclusively found in the inner mitochondrial membrane that is essential for the structural organization and function of the electron transport chain (ETC) complexes. Cardiolipin normally interacts with cytochrome c to facilitate efficient electron transfer. However, oxidative stress, aging, and disease cause cardiolipin peroxidation, disrupting ETC supercomplex assembly and increasing electron leak (generating more reactive oxygen species in a vicious cycle). SS-31 binds to cardiolipin and stabilizes its interaction with cytochrome c, restoring efficient electron flow through Complex III and IV. This reduces electron leak, decreases mitochondrial ROS production by 30–50%, and improves ATP synthesis. Critically, SS-31 does not act as a conventional antioxidant (it doesn't scavenge free radicals) — instead, it prevents excess ROS generation at the source by optimizing ETC function. It also protects against mitochondrial permeability transition pore opening, preventing apoptotic signaling.

• EMBRACE trial (2019, JAMA Cardiology): SS-31 (elamipretide) showed trends toward improved cardiac function in patients with acute ST-elevation MI
• TAZPOWER trial in Barth syndrome showed significant improvements in 6-minute walk distance and cardiac function
• Siegel et al. (2013, PNAS) demonstrated SS-31 reversed age-related mitochondrial dysfunction and improved skeletal muscle performance in old mice
• SS-31 reduced mitochondrial ROS by 30–50% in cardiomyocytes and improved ATP production by 30% in aged mitochondria
• Studies in renal ischemia-reperfusion models showed SS-31 prevented acute kidney injury and preserved tubular function
• Campbell et al. (2019, Aging Cell) showed SS-31 improved vascular endothelial function in aged mice by restoring mitochondrial health

• Clinical trial dose (heart failure): 4 mg/hour IV infusion for 1 hour, or 40 mg SC daily
• Barth syndrome trials: 40 mg SC daily for up to 168 weeks
• Research protocols: 0.5–5 mg/kg subcutaneous injection daily
• Some anti-aging protocols use 1–5 mg subcutaneous injection daily or every other day
• No established oral dosing — peptide requires parenteral administration
• Cycle: clinical trials have used continuous dosing for up to 3+ years without safety concerns

Known Side Effects

• Injection site reactions (redness, pain) are the most commonly reported side effect in clinical trials
• Headache reported in some trial participants
• Mild GI symptoms (nausea) at higher doses
• Clinical trials have shown a generally favorable tolerability profile
• No significant organ toxicity observed in studies up to 168 weeks
• Theoretical concern about altering mitochondrial dynamics in rapidly dividing cells

Safety Profile

SS-31 (elamipretide) has undergone multiple Phase I–III clinical trials with a favorable safety record. The Barth syndrome TAZPOWER extension study provided long-term safety data over 168+ weeks of daily SC dosing without emergent safety signals. The most common adverse events are injection site reactions and headache. No clinically significant effects on hematology, liver function, or renal function have been observed. The compound does not appear to accumulate or cause tolerance with chronic use. However, the FDA has issued a Complete Response Letter for the Barth syndrome indication, requesting additional efficacy data, though safety was not the concern. SS-31 is not yet FDA-approved for any indication. Contraindications are not well-established; general caution is advised in patients with mitochondrial proliferative disorders.

Week 1–2: Effects on mitochondrial function begin immediately at the cellular level but subjective improvements are subtle. Some users report improved energy levels and exercise recovery. Week 2–4: Improved exercise tolerance and reduced post-exertion fatigue become more noticeable. Cellular energy production improves. Week 4–8: Sustained energy improvements, better cardiovascular endurance, and improved recovery from physical and mental exertion. In clinical settings, measurable improvements in 6-minute walk distance and cardiac output have been observed. Week 8+: Continued optimization of mitochondrial function. In aging populations, benefits may include improved cognitive clarity, vascular function, and physical performance. Long-term users report sustained benefits without tolerance.

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