SS-31 Calculator

What Is SS-31 (Elamipretide)?

SS-31, also known by its clinical development name elamipretide and the research designation MTP-131, is a synthetic tetrapeptide developed by Hazel Szeto and Peter Schiller at Weill Cornell Medical College in the early 2000s. The sequence is D-Arg-dimethylTyr-Lys-Phe-NH2 — a cell-permeable, mitochondria-targeted peptide belonging to the Szeto-Schiller (SS) family of compounds.

SS-31 is unique among research peptides in its ability to selectively concentrate in the inner mitochondrial membrane (IMM), where it binds with high affinity to cardiolipin — a phospholipid found almost exclusively in the IMM and essential for the structural integrity of the electron transport chain (ETC). This specific mechanism of action places SS-31 in a class of its own: it is not a signaling peptide acting through cell-surface receptors, but a membrane-targeted therapeutic that physically restores mitochondrial architecture.

Clinically, SS-31 (as elamipretide) has been the subject of Phase II and Phase III trials for Barth syndrome — a rare genetic disorder caused by mutations in the tafazzin gene that result in abnormal cardiolipin remodeling and consequent mitochondrial dysfunction. The drug received Orphan Drug and Breakthrough Therapy designation from the FDA. Beyond Barth syndrome, SS-31 has been studied in models of heart failure, renal ischemia-reperfusion injury, neurodegenerative disease, and aging.

Mechanism of Action

SS-31's mechanism is centered on cardiolipin, a structurally critical phospholipid of the inner mitochondrial membrane:

• Cardiolipin binding and structural stabilization: Cardiolipin is organized in tightly packed clusters in the IMM and functions as a scaffold for the supercomplexes of the electron transport chain (complexes I, III, and IV). In aged, diseased, or damaged mitochondria, cardiolipin undergoes peroxidation — oxidative damage that disrupts the structural integrity of ETC supercomplexes. SS-31 binds to cardiolipin via electrostatic and hydrophobic interactions, protecting it from peroxidation and maintaining supercomplex architecture.
• Electron transport chain efficiency: By preserving ETC supercomplex organization, SS-31 restores the efficiency of electron flow from NADH and FADH2 to the terminal electron acceptor oxygen. This translates to increased ATP production per unit of substrate, improved mitochondrial membrane potential, and reduced electron leak — the latter being the primary source of mitochondrial superoxide.
• Reactive oxygen species (ROS) reduction: Electron leak at complexes I and III generates superoxide, which drives oxidative damage cascades in mitochondria and throughout the cell. By reducing electron leak through ETC supercomplex stabilization, SS-31 dramatically reduces mitochondrial ROS production. Studies in aged tissue show 2–5 fold reductions in mitochondrial H2O2 emission following SS-31 treatment.
• Cristae remodeling: SS-31 promotes the maintenance of cristae morphology — the internal folded membrane structures of mitochondria where the ETC is embedded. Cristae collapse is a hallmark of mitochondrial aging and dysfunction. Restoring cristae morphology amplifies the benefits at the ETC level by physically concentrating respiratory chain complexes.
• Cytochrome c retention: In apoptotic signaling, cytochrome c is released from the IMM as an early event. SS-31 stabilizes the cardiolipin-cytochrome c interaction, preventing premature cytochrome c release and apoptotic cascade initiation in stressed cells — a potentially important mechanism in both neuronal and cardiac preservation.

Dosage and Dosing Protocol

SS-31 research dosing in humans is extrapolated primarily from animal studies and from the clinical trial dosing used in Barth syndrome research. Use the SS-31 Calculator to determine exact volumes for your reconstituted vial.

Typical Dosing Range

• Conservative starting dose: 0.1–0.25 mg per day subcutaneous
• Standard research dose: 0.5 mg per day subcutaneous
• Higher range: 0.75–1 mg per day subcutaneous

Protocol Structure

SS-31 is typically dosed once daily:

• Frequency: Once daily subcutaneous injection. Given the approximately 4-hour half-life, daily dosing maintains consistent tissue exposure. Some protocols use twice-daily dosing for higher-intensity applications, though once daily is standard.
• Injection site: Subcutaneous injection into the abdomen, lateral thigh, or upper arm. Rotate sites to prevent injection site reactions.
• Cycle length: Most protocols run 8–12 weeks. Unlike peptides targeting hormonal axes, SS-31 does not produce receptor downregulation or rebound phenomena. Extended use has been studied in clinical contexts without evidence of diminishing effect.
• Timing: Morning administration is commonly used; there is no strong evidence favoring any specific time of day for SS-31.

A standard 5 mg vial reconstituted with 2 mL BAC water yields 2.5 mg/mL. At this concentration, a 0.5 mg dose = 0.20 mL (200 µL) drawn into a 0.3 mL insulin syringe. View SS-31 at BergdorfBio for purchasing options.

Reconstitution

SS-31 is supplied as lyophilized powder, typically in 5 mg or 10 mg vials. Reconstitute with bacteriostatic water (BAC water) as follows:

1. Allow the vial to reach room temperature before reconstitution (15–20 minutes out of the refrigerator or freezer).
2. Clean the rubber stopper of both the peptide vial and the BAC water vial with a 70% isopropyl alcohol swab. Allow to dry completely.
3. Draw 2 mL of BAC water into a sterile syringe:
   • For a 5 mg vial: yields 2.5 mg/mL
   • For a 10 mg vial: yields 5 mg/mL
4. Angle the needle against the inner glass wall and slowly depress the plunger so that BAC water trickles down the side — do not inject directly onto the lyophilized powder.
5. Gently swirl (do not shake or vortex) until the powder is fully dissolved. The solution should be clear and colorless.
6. Label the vial with the reconstitution date and concentration.

SS-31 reconstitutes readily and does not require extended mixing. Use the SS-31 Peptide Calculator to compute exact draw volumes for any dose and vial concentration combination.

Storage and Shelf Life

• Lyophilized powder (unreconstituted): Store at −20°C for long-term stability (up to 24 months). Short-term refrigerator storage (4°C) is acceptable for up to 3 months. Protect from light, moisture, and temperature fluctuations.
• Reconstituted solution: Store at 2–8°C (refrigerator). Use within 28–30 days of reconstitution. Keep upright and away from direct light. Do not freeze the reconstituted solution — freeze-thaw cycles degrade the peptide.
• Transport: Use an insulated cooler bag with ice pack. SS-31 is reasonably stable at room temperature for brief periods (hours), but sustained exposure above 25°C should be avoided.
• Vial integrity: Discard any reconstituted solution that appears cloudy, colored, or contains particulate matter.

Side Effects and Safety

SS-31 has a well-characterized preclinical safety profile and has been evaluated in multiple human clinical trials as elamipretide. The overall safety record is favorable.

Clinically Observed Effects

• Injection site reactions: The most consistently reported adverse effect in clinical trials is injection site reaction — erythema, induration, pruritus, or pain at the site of subcutaneous injection. These are typically mild, dose-dependent, and resolve within 24–48 hours. Site rotation minimizes their frequency.
• Transient hypotension: Mild, transient reductions in blood pressure have been observed in some Barth syndrome trial participants, likely related to improved cardiac output and reduced systemic vascular resistance. For most healthy research subjects at standard doses, this is not clinically significant.
• Fatigue: Occasionally reported in clinical studies, though it is difficult to separate from underlying disease states in the trial populations. Longitudinal self-reports from research protocols more typically report improved energy rather than fatigue.

Precautions

• Individuals with cardiovascular conditions, particularly those on antihypertensive medications, should monitor blood pressure when beginning an SS-31 protocol, given the peptide's effects on cardiac and vascular function.
• No clinical data exists for SS-31 use during pregnancy or breastfeeding. Avoid use in these populations.
• SS-31 is not immunosuppressive and does not interact with hormonal axes. No PCT is required after a cycle.

In Phase I pharmacokinetic studies, SS-31 was well tolerated at single doses up to 0.25 mg/kg in healthy volunteers. No dose-limiting toxicities, organ toxicity, or serious adverse events were reported at research-relevant doses.

Combinations and Stacks

SS-31 + MOTS-c (Mitochondrial Longevity Stack)

The most mechanistically coherent SS-31 stack pairs it with MOTS-c. SS-31 addresses structural damage in the inner mitochondrial membrane — restoring cardiolipin integrity, ETC supercomplex function, and reducing ROS. MOTS-c addresses mitochondrial signaling deficits — activating AMPK, upregulating PGC-1α-driven biogenesis, and improving systemic metabolic efficiency. Together they form a complete mitochondrial rehabilitation protocol: structural repair (SS-31) plus functional reprogramming (MOTS-c).

• SS-31: 0.5 mg subcutaneous, once daily
• MOTS-c: 5–10 mg subcutaneous, once weekly
• Cycle: 8–12 weeks with 4-week washout

SS-31 + Selank (Neuroprotection and Cognition Stack)

For researchers focused on brain health, the combination of SS-31 and Selank addresses mitochondrial neuronal aging alongside anxiolytic and neuroplasticity support. Neuronal mitochondria are among the most metabolically demanding in the body and among the most affected by age-related cardiolipin peroxidation. SS-31 addresses this at the structural level while Selank enhances BDNF, reduces cortisol stress burden, and supports GABAergic tone. For cognitive longevity or stress-related cognitive decline, this is a well-reasoned combination.

SS-31 Alone: When Structure Is the Priority

For individuals with a clear mitochondrial dysfunction focus — post-ischemic recovery, Barth syndrome research, heart failure models, or general mitochondrial aging — SS-31 as a standalone protocol is well supported by existing data. Its highly specific mechanism means it does not require supporting peptides to achieve its primary target, though the combinations above broaden its scope.

Frequently Asked Questions

How is SS-31 different from CoQ10 or MitoQ for mitochondrial health?

Coenzyme Q10 and MitoQ are lipophilic antioxidants that reduce mitochondrial ROS by accepting electrons. SS-31 works differently — it does not function primarily as an antioxidant but as a structural stabilizer of cardiolipin. By preventing cardiolipin peroxidation, SS-31 addresses the upstream cause of ETC dysfunction and ROS generation rather than downstream consequences. Studies directly comparing SS-31 with mitochondrial antioxidants in aged tissue consistently show superior outcomes for SS-31 in restoring ETC function and mitochondrial membrane potential.

What is Barth syndrome, and why is it relevant to SS-31 research?

Barth syndrome is a rare X-linked genetic disorder caused by mutations in the tafazzin (TAZ) gene, which encodes an enzyme essential for cardiolipin remodeling. The result is structurally abnormal cardiolipin that cannot support ETC supercomplex integrity, causing severe mitochondrial cardiomyopathy, skeletal muscle weakness, and immunodeficiency. Because SS-31 targets cardiolipin directly, Barth syndrome is the most mechanistically precise clinical indication for elamipretide, and the clinical trial data from Barth syndrome informs dosing and safety assumptions for broader research use.

How quickly does SS-31 produce measurable mitochondrial improvements?

In animal studies, significant improvements in mitochondrial respiration and ROS reduction are measurable within 1–2 hours of acute administration. With chronic dosing, structural improvements in cristae morphology and ETC organization are observed within 2–4 weeks. Human researchers in non-clinical settings typically report subjective improvements in energy levels and exercise recovery within 3–6 weeks.

Does SS-31 have cardiac-specific benefits?

Yes. The cardiac application of SS-31 is one of its best-studied areas. In heart failure models, SS-31 restores mitochondrial bioenergetics in cardiomyocytes, reduces oxidative stress, improves systolic function, and reduces pathological cardiac remodeling. In clinical trials for Barth syndrome cardiomyopathy, improvements in exercise capacity, cardiac function, and quality of life have been documented. The peptide is sometimes used by researchers focusing specifically on cardiovascular longevity.

Does SS-31 accumulate in the mitochondria, or does it require repeated dosing?

SS-31 does not permanently accumulate in mitochondria — it distributes rapidly to the inner mitochondrial membrane following subcutaneous injection and is cleared with a half-life of approximately 4 hours. Its benefits are therefore sustained through regular dosing rather than through accumulation. This is consistent with its status as a membrane-stabilizing agent rather than a gene expression modifier.

Can SS-31 be used for renal protection?

Renal tubular cells are among the most mitochondria-dense cells in the body and are highly susceptible to ischemia-reperfusion injury. Multiple preclinical studies have demonstrated SS-31's ability to protect renal tissue from ischemic damage, reduce acute kidney injury severity, and preserve renal function. Some researchers investigating nephroprotective protocols include SS-31 based on this body of evidence.

Is SS-31 suitable for neurological applications?

Yes. Neuronal mitochondrial dysfunction is implicated in Alzheimer's disease, Parkinson's disease, ALS, and general cognitive aging. SS-31 has shown neuroprotective effects in multiple preclinical models of these conditions, reducing mitochondrial ROS, preserving synaptic function, and improving neuronal survival. It has been studied specifically in the context of Alzheimer's-related mitochondrial dysfunction, where amyloid-beta-induced cardiolipin peroxidation is a key mechanism.

What syringe should I use for SS-31 injections?

Given the typical dose of 0.5 mg and a concentration of 2.5 mg/mL (volume = 0.20 mL), a 0.3 mL or 0.5 mL insulin syringe with a 29–31 gauge, 0.5-inch needle is ideal. The small volume allows precise measurement and comfortable subcutaneous delivery.

Medical Disclaimer: The information on this page is provided for educational and research purposes only. SS-31 (elamipretide) is not an approved drug for general use. It is sold strictly for research purposes. Nothing on this page constitutes medical advice, diagnosis, or a recommendation to use any specific compound. Always consult a qualified healthcare professional before beginning any peptide protocol. BergdorfBio assumes no liability for the use or misuse of the information presented here.