Health & Research Goals
SS-31 (Elamipretide / MTP-131)
SS-31 (Elamipretida / MTP-131)
SS-31, also known as Elamipretide or MTP-131, is a mitochondria-targeted tetrapeptide (D-Arg-2',6'-Dmt-Lys-Phe-NH2) developed by H…
Primary Description
SS-31, also known as Elamipretide or MTP-131, is a mitochondria-targeted tetrapeptide (D-Arg-2',6'-Dmt-Lys-Phe-NH2) developed by Hazel Szeto and Peter Schiller. It belongs to the Szeto-Schiller (SS) peptide class, designed to selectively concentrate in the inner mitochondrial membrane where it interacts with cardiolipin — a phospholipid critical for the electron transport chain and mitochondrial cristae structure. SS-31 stabilizes cardiolipin-cytochrome c interactions, improving mitochondrial membrane integrity, restoring electron transport chain efficiency, reducing reactive oxygen species (ROS) production, and preventing apoptosis. SS-31 is one of the most potent mitochondria-targeted antioxidants known, with a 1,000-fold concentration factor in the inner mitochondrial membrane. It has been investigated in clinical trials for heart failure, aging, ischemia-reperfusion injury, and multiple diseases of mitochondrial dysfunction.
Key Benefits
- Mitochondrial function
- Cardioprotection
- Exercise capacity
Store lyophilized powder at -20°C for long-term storage, or 2–8°C for short-term. Reconstituted solution: use promptly or refrigerate and use within 7–14 days. Protect from light. Sensitive to oxidation — reconstitute immediately before use when possible.
Demonstrated Effects
- Potent mitochondria-targeted antioxidant — concentrates 1,000-fold in inner mitochondrial membrane
- Stabilizes cardiolipin preventing mitochondrial cristae collapse
- Restores electron transport chain efficiency and ATP production
- Reduces mitochondrial reactive oxygen species (ROS) generation
- Prevents mitochondria-mediated apoptosis (cell death)
- Improves exercise capacity in heart failure patients (clinical trial data)
- Protects against ischemia-reperfusion injury in heart, kidney, and brain
- Potentially reverses age-related mitochondrial dysfunction
- Investigated for Barth syndrome (genetic cardiolipin metabolism disorder)
- May improve skeletal muscle bioenergetics and exercise tolerance in aging
Proposed Mechanisms of Action
1. Cardiolipin Stabilization
SS-31 selectively localizes to the inner mitochondrial membrane and binds cardiolipin — a unique phospholipid essential for cristae structure and the electron transport chain. By stabilizing cardiolipin, SS-31 preserves mitochondrial architecture and prevents cytochrome c release.
2. Electron Transport Chain Optimization
Cardiolipin is required for optimal function of Complex I, III, IV, and V (ATP synthase). SS-31's stabilization of cardiolipin restores electron transfer efficiency, reducing electron leak and ROS generation while improving ATP production.
3. Reactive Oxygen Species Scavenging
The aromatic-cationic structure of SS-31 provides direct antioxidant activity, scavenging mitochondrial ROS generated by the electron transport chain — particularly superoxide and hydrogen peroxide.
4. Prevention of Apoptosis
By preventing cardiolipin oxidation and cytochrome c release, SS-31 blocks the mitochondrial pathway of apoptosis — critical in ischemia-reperfusion injury and age-related cell death.
5. Mitochondrial Biogenesis Support
Improved mitochondrial health from SS-31 treatment may secondarily support mitochondrial biogenesis pathways, though this is not the primary direct mechanism.
Research Evidence & Clinical Data
Investigated Applications
Heart Failure and Cardiac Function
Anecdotal: ModerateSS-31 (Elamipretide) entered Phase 2 clinical trials for heart failure with reduced ejection fraction (HFrEF). The PROGRESS-HF trial showed improvements in left ventricular remodeling and some functional endpoints. Cardiolipin is especially abundant in cardiomyocytes, making the heart a primary target tissue.
Preclinical basis: Multiple preclinical studies show SS-31 prevents ischemia-reperfusion cardiac injury, preserves ejection fraction, and reduces infarct size. Phase 2 clinical data (PROGRESS-HF) showed remodeling benefits.
Anti-Aging and Mitochondrial Longevity
Anecdotal: EmergingMitochondrial dysfunction is a central hallmark of aging. SS-31's ability to restore mitochondrial structure and function in aged tissue makes it one of the most mechanistically compelling longevity compounds. Aged rodents treated with SS-31 show restoration of mitochondrial morphology and function toward younger profiles.
Preclinical basis: Siegel et al. (2013, JACS): SS-31 reverses age-related mitochondrial morphological changes. Chavez et al. (2020): Elamipretide reverses age-related skeletal muscle mitochondrial dysfunction.
Exercise Capacity and Muscle Bioenergetics
Anecdotal: ModerateBy restoring mitochondrial efficiency in skeletal muscle, SS-31 has been shown to improve exercise capacity in both aging and disease models. Clinical trial in elderly subjects (REACH trial) demonstrated improved mitochondrial energetics and physical performance.
Preclinical basis: Siegel MP et al. (2013): SS-31 improved mitochondrial function and decreased reactive oxygen species in aged skeletal muscle with corresponding improvements in physical performance.
Kidney Protection
Anecdotal: EmergingSS-31 has been extensively studied for renal ischemia-reperfusion injury protection and chronic kidney disease. Cardiolipin is abundant in renal tubular cells, and SS-31 protects against contrast-induced nephropathy and surgical kidney injury.
Preclinical basis: Multiple animal studies demonstrate significant renal protection from ischemia-reperfusion injury with SS-31 treatment.
Scientific References
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Safety Profile
Common Side Effects
- Injection site reactions (mild redness, irritation)
- Transient flushing (rare)
- Headache (infrequent)
- Injection site reactions
Contraindications
- Hypersensitivity to any component
- Pregnancy and breastfeeding (insufficient data)
- Active malignancy (precaution — insufficient data)
- Children (insufficient safety data)
- None well-established
Legal & Regulatory Status
Elamipretide (SS-31) is an investigational drug (IND) that has completed Phase 1 and Phase 2 clinical trials in the US for heart failure, Barth syndrome, and other mitochondrial disorders. Not yet FDA-approved. Available as a research compound from peptide vendors. Not a controlled substance.
Elamipretida (SS-31) es un fármaco investigacional (IND) que ha completado ensayos clínicos de Fase 1 y Fase 2 en EE. UU. para insuficiencia cardíaca, síndrome de Barth y otros trastornos mitocondriales. No aprobado aún por la FDA. Disponible como compuesto de investigación de proveedores de péptidos. No es una sustancia controlada.
Research Protocols
Dosing Protocols
Routes of Administration
subcutaneous
intravenous (clinical research)
Reconstitution Guide
Pharmacokinetics
| Half-Life | Approximately 30–60 minutes in plasma. Despite short plasma half-life, effects persist due to high-affinity cardiolipin binding and prolonged mitochondrial retention. |
Monitoring & Risk Management
Ongoing Monitoring Steps
- Renal function monitoring (creatinine, eGFR) every 4–6 weeks
- Blood pressure
- Subjective energy, exercise tolerance, and recovery assessment
- Cardiac monitoring if cardiac indication
Critical Warning Signs
- Significant hypotension
- Severe injection site reactions
- Unexplained fatigue or muscle weakness (rare)
- Any allergic reaction symptoms
Featured in Stacking Protocols
Community-researched combinations involving this compound