WHAT IS SS-31

SS-31 (Elamipretide) is a synthetic tetrapeptide (composed of four amino acids) with the sequence D-Arg-Dmt-Lys-Phe-NH2.  It belongs to a class of Mitochondria-Targeted Therapeutics (MTTs) known as aromatic-cationic peptides. 

Unlike many other peptides that work on surface receptors, SS-31 was engineered to specifically target the mitochondria—the energy-producing organelles inside cells. This makes it one of the most direct tools for addressing mitochondrial dysfunction.

•  Target: What makes SS-31 unique is its high affinity for cardiolipin, a phospholipid found in the inner mitochondrial membrane that is essential for maintaining mitochondrial structure and energy production. 

•  Action: By binding directly to cardiolipin, SS-31 protects the integrity of the mitochondrial membrane and helps optimize cellular energy output.  It was specifically engineered to penetrate the cellular outer membrane and selectively accumulate within the mitochondria. 

WHAT DOES SS-31 DO?

The power of SS-31 lies in its direct targeting of mitochondria, making it one of the few peptides that works inside the cell’s energy center rather than on surface receptors. SS-31 functions as a structural stabilizer and antioxidant within the powerhouse of the cell, correcting the underlying energetic deficits associated with aging and disease.

Key Mitochondrial Actions

• Cardiolipin Stabilization: SS-31 selectively targets and binds to Cardiolipin (CL), a unique phospholipid found almost exclusively in the inner mitochondrial membrane (IMM). This binding stabilizes the IMM structure, maintaining the optimal organization of the Electron Transport Chain (ETC) supercomplexes for efficient ATP production.

• ROS Scavenging: It acts as a powerful antioxidant at the source of Reactive Oxygen Species (ROS) generation (the IMM), directly mitigating oxidative stress and preventing Cardiolipin peroxidation.

• mPTP Inhibition: SS-31 reduces the opening of the Mitochondrial Permeability Transition Pore (mPTP). This pore opening is a critical event leading to mitochondrial membrane potential collapse and apoptosis (cell death) during cellular stress (EX: calcium overload).

BENEFITS/ CLINICAL TRIALS

SS-31 functions as a structural stabilizer and antioxidant within the powerhouse of the cell, correcting the underlying energetic deficits associated with aging and disease. The power of SS-31 lies in its direct targeting of mitochondria, making it one of the few peptides that works inside the cell’s energy center rather than on surface receptors.

Mechanism of Action and Cellular Effects

SS-31's actions revolve around protecting and optimizing mitochondrial function, which influences energy, recovery, and cellular health.

1. Cardiolipin Stabilization: SS-31 has a strong affinity for cardiolipin, a phospholipid unique to the inner mitochondrial membrane (IMM). By binding to cardiolipin, SS-31 stabilizes the mitochondrial membrane and prevents structural damage. Cardiolipin is critical for maintaining mitochondrial structure and supporting the electron transport chain (ETC).

2. Improves Electron Transport Efficiency: SS-31 optimizes the organization of the ETC supercomplexes, where ATP is produced, reducing electron “leakage” that causes inefficiency. This leads to improved ATP production and greater energy availability at the cellular level.

3. Reduces Oxidative Stress: By stabilizing the ETC and cardiolipin, SS-31 reduces Reactive Oxygen Species (ROS) generation at the source. This limits oxidative stress and protects surrounding tissues from chronic inflammation and aging.

4. Cellular Bioenergetics: Increases the overall output of ATP, enhancing the cell's energy to perform vital processes. This supports tissues with high energy demand, including the heart, brain, skeletal muscle, and nervous system, and may improve endurance, recovery, and resistance to fatigue.

5. Protects Against Mitochondrial Dysfunction: SS-31 preserves mitochondrial function even under stress, making it a potential therapeutic tool in both medicine and performance applications.

Key Benefits Observed in Research Models

SS-31 has been investigated across a remarkably broad range of conditions where mitochondrial dysfunction is implicated.

• Renal Protection (Kidneys): Promising results in models of Acute Kidney Injury (AKI) caused by ischemia reperfusion. SS-31 preserved mitochondrial structure, restored ATP supply, and reduced tubular necrosis. Long term studies showed sustained protection against chronic fibrosis and damage.

• Cardiovascular Health: Preclinical data shows SS-31 treatment reverses age related decline in cardiac diastolic function and reduces atherosclerotic plaque area in mouse models, linking to improved mitochondrial energetics in the heart.

• Neuroprotection: Provides protection against secondary brain injury following Traumatic Brain Injury (TBI), stroke, and neurodegenerative pathology (EX: reduces DNA damage and neuronal apoptosis).

• Metabolic Health: Protects the kidney against high glucose induced injury in models of diabetic nephropathy via its antioxidant mechanisms.

Clinical Trial Findings 

• Status: SS-31 (Elamipretide) is currently or has been in Phase 2 and Phase 3 clinical trials for several conditions, including Primary Mitochondrial Myopathy (PMM), Barth syndrome, and Heart Failure.

• Results Summary: While early Phase 2 trials showed promising functional improvements (EX: increased distance walked in the 6 minute walk test in PMM patients), large Phase 3 trials have been complex and have sometimes failed to meet primary endpoints, underscoring the challenge of treating complex mitochondrial disorders.

SIDE EFFECTS

SS-31 has an exceptional safety profile, with adverse events typically mild and localized, particularly when compared to its potent mechanism of action.

Side Effects (Mild and Localized)

• Injection Site Reactions (Most Common): These are the most frequently reported adverse events in clinical trials, experienced by approximately 80 percent of patients. Reactions include mild-to-moderate redness, itching, pain, or transient discomfort at the injection site. These typically resolve within hours.

• Systemic Effects: SS-31 is generally well-tolerated with minimal systemic toxicity observed across extensive preclinical and early human studies.

Safety Status

• Toxicity: No dose-limiting toxicities or serious adverse events have been directly attributed to SS-31 in published trials.

• Long-Term Safety: Long-term safety is still being established through ongoing trials, as continuous treatment duration has been studied up to 36 weeks. Long term safety data beyond 12 weeks remains limited; extended use requires monitoring.

IS SS-31 SAFE?  

SS-31 (Elamipretide) is an investigational pharmaceutical drug and is not FDA-approved for therapeutic use.

Safety Profile Summary

• Favorable Safety: SS-31 has been evaluated in multiple clinical and preclinical studies, with findings showing a generally favorable safety profile. 

•  Targeted Action: It is considered one of the safest experimental peptides currently in development, based on its selective targeting of dysfunctional mitochondria and its lack of severe systemic toxicity.  Because it is mitochondria-specific and does not interact with hormonal pathways, it tends to be well tolerated.  

• Limitations: Still, understanding its potential side effects and limitations is critical.

• Safety Takeaway: However, its use remains restricted to clinical research settings until Phase 3 data can confirm efficacy and long term safety for chronic use.

DOSAGE

Dosing for SS-31 is based on rigorous clinical trial protocols and is measured in milligrams (mg). Since SS-31 is not FDA-approved, there are no standardized clinical dosing guidelines outside of investigational studies.

Administration and Frequency

• Administration: Typically administered via Subcutaneous (SubQ) injection once daily. Intravenous (IV) infusion was used in earlier dose-escalation studies.

• Research Frequency: Research settings often use daily or every-other-day injections.

Clinical and Research Dosing 

• Phase 3 Clinical Trial Dose: The standard dose used in Phase 3 trials for PMM and Heart Failure research is 40 mg SubQ once daily.

• Research Dosing (General): Dosage varies depending on the condition studied, but ranges in human trials have generally fallen within the single-digit milligram scale per day.

• Preclinical Protocol Dose (Animal): Preclinical animal studies typically use mg/kg doses (EX: 5 mg/kg IP) for neuroprotection.

Example Research Protocol 

This example reflects protocols for assessing initial human tolerance (note: the syringe measurements below assume a specific reconstitution concentration, typically 10 mg/mL, which yields 100 units = 1.0 mL).

• Weeks 1–2 (Starting Dose): 5 mg (5,000 mcg)

• Weeks 3–8: 10 mg (10,000 mcg)

RECONSTITUTION

SS-31 (Elamipretide) is supplied as a lyophilized (freeze-dried) powder for compounding or injection use. 

• Reconstitution Fluid: Use sterile or bacteriostatic water (BAC Water) or saline.

• Target Dilution (EX: 50 mg Vial): Draw 5.0 mL bacteriostatic water with a sterile syringe for a 50 mg vial. This yields a common, high-concentration solution of 10 mg/mL.

• Standard Dilution (EX: 10 mg Vial): For a 10 mg vial, adding 1 mL of BAC water results in a concentration of 10 mg/mL.

• Mixing Technique: Inject the BAC Water slowly down the side of the vial. DO NOT SHAKE vigorously. Gently swirl the vial until the powder is completely dissolved into a clear solution.

Post-Reconstitution Storage 

• Storage: Once reconstituted, the solution must be stored in the refrigerator (2°C to 8°C).

• Stability: The solution is typically stable for 14 to 28 days under proper refrigeration.

WHERE TO BUY SS-31

Researchers should always vet their sources to ensure that a few key factors are present in their test subjects. With the rise in peptide popularity in recent years, many companies have created peptides that undergo little to no testing, quality standards, or regulations. As it is not regulated by the FDA, researchers must do their due diligence and look closely at the company's practices and standards. 

When selecting a supplier for SS-31, focus on transparency and quality assurance, not customer testimonials:

1. Quality Documentation: A reputable supplier must provide:
   •  Certificate of Analysis (COA): This document must be recent (corresponding to the batch/lot number purchased) and demonstrate a minimum purity of >95% via High-Performance Liquid Chromatography (HPLC) testing.
   • Mass Spectrometry (MS) Data: The COA must include mass spectrometry (MS) confirmation to verify the compound’s exact molecular weight, confirming its chemical identity.
   • Contaminant Testing: Look for reports on heavy metals, microbial load, and solvent residues (e.g., residual trifluoroacetic acid, or TFA). The presence of these contaminants can severely compromise research and introduce unknown toxicity.
2. Vendor Verification and Transparency 

   • Specialization: Prioritize vendors who specialize in the manufacturing and distribution of peptides for academic and biotechnology research, rather than general supplement vendors.

   • Manufacturing Origin: Inquire about the source of the raw materials and the manufacturing protocols. Ideal suppliers adhere to strict quality control processes.

   • Handling & Storage: The supplier must provide clear documentation on the proper storage and handling procedures for the peptide to maintain its stability and integrity.

Conclusion on Procurement: Given the high risk of contamination, mislabeling, and legal ambiguity. The use of SS-31 outside of this defined research context poses unacceptable, unquantified risks to human health.

REFERENCES

• Russo, Silvia, et al. “Beneficial Effects of SS-31 Peptide on Cardiac Mitochondrial Dysfunction in Tafazzin Knockdown Mice.” Nature News, Nature Publishing Group, 18 Nov. 2022, www.nature.com/articles/s41598-022-24231-4. 
• “SS-31 (30mg Vial) Dosage Protocol.” Peptidedosages.Com, 22 Nov. 2025, peptidedosages.com/single-peptide-dosages/ss-31-30mg-vial-dosage-protocol/. 
• by, Written. “SS-31 Peptide (Elamipretide): Benefits, Dosage, Side Effects.” Swolverine, swolverine.com/blogs/blog/ss-31-peptide-mitochondrial-protection-and-performance-potential?_pos=1&_sid=09997f133&_ss=r. Accessed 25 Nov. 2025.

• PNAS (ID 10.1073/pnas.2002250117). "$\text{Mitochondrial}$ $\text{protein}$ $\text{interaction}$ $\text{landscape}$ of $\text{SS-31}$."

• American Physiological Society Journal. "$\text{Mitochondria-targeted}$ $\text{peptide}$ $\text{SS-31}$ $\text{attenuates}$ $\text{renal}$ $\text{injury}$ via $\text{an}$ $\text{antioxidant}$ $\text{effect}$ in $\text{diabetic}$ $\text{nephropathy}$."

• eLife (ID 55513). "$\text{Late-life}$ $\text{restoration}$ of $\text{mitochondrial}$ $\text{function}$ $\text{reverses}$ $\text{cardiac}$ $\text{dysfunction}$ in $\text{old}$ $\text{mice}$."

• PubMed Central (PMC6129854). "$\text{SS-31}$ $\text{Provides}$ $\text{Neuroprotection}$ $\text{by}$ $\text{Reversing}$ $\text{Mitochondrial}$ $\text{Dysfunction}$ $\text{after}$ $\text{Traumatic}$ $\text{Brain}$ $\text{Injury}$."

• Dr.Oracle. "What is the $\text{recommended}$ $\text{dosing}$ $\text{regimen}$ for $\text{Elamipretide}$ ($\text{SS}31$)?".

• PLOS $\text{One}$ (ID 10.1371/journal.pone.0185688). "$\text{Chronic}$ $\text{administration}$ of $\text{mitochondrion-targeted}$ $\text{peptide}$ $\text{SS-31}$ $\text{prevents}$ $\text{atherosclerotic}$ $\text{development}$ $\text{in}$ $\text{ApoE}$ $\text{knockout}$ $\text{mice}$..."