SS-31
Elamipretide · Elamipretide · MTP-131 · Bendavia · Forzinity · D-Arg-Dmt-Lys-Phe-NH2
Cardiolipin-binding mitochondrial peptide, FDA-approved as elamipretide for Barth syndrome.
Typical dose
10 mg
Once daily
Range
5–40
mg
Half-life
2 h
see Dosing
Evidence
Human trials
Subcutaneous · Intravenous
What it is
SS-31 is a synthetic aromatic-cationic tetrapeptide developed by Hazel Szeto and Peter Schiller. It is the only compound in this group with real clinical development behind it: as elamipretide it ran through phase 1, 2 and 3 trials in primary mitochondrial myopathy, Barth syndrome, dry AMD and heart failure, and in September 2025 the FDA granted it accelerated approval as Forzinity for Barth syndrome.
Its distinguishing property is targeting. Rather than acting as a general antioxidant, SS-31 concentrates in the inner mitochondrial membrane at concentrations roughly a thousand-fold above plasma, where it binds cardiolipin — the signature phospholipid that holds the electron transport chain in working order. Damaged cardiolipin is a common endpoint of ageing, ischaemia and mitochondrial disease.
The trial record is honest but mixed. The randomised phases of BOTH the Barth trial (TAZPOWER) and the large MMPOWER-3 myopathy trial missed their primary endpoints; the accelerated approval rested on knee-extensor muscle-strength gains during the Barth open-label extension measured against a natural-history comparison, and the heart-failure programme was discontinued. It is a real drug with a real mechanism, not a cure-all, and the community dose is typically well below the approved one.
How it works
SS-31 carries an alternating aromatic-cationic motif that lets it cross membranes without a transporter and lodge in the inner mitochondrial membrane, where its positive charge pairs with the negatively charged head groups of cardiolipin. Stabilising cardiolipin keeps cytochrome c bound in its electron-carrying role rather than leaking into the cytosol as a peroxidase and apoptosis trigger, and keeps the respiratory supercomplexes assembled.
The downstream result is more ATP per unit of oxygen and less electron leak into reactive oxygen species — it improves the efficiency of mitochondria that are already damaged rather than building new ones. That is why the strongest responses are seen in tissue with genuine mitochondrial dysfunction, and why healthy young users often report very little.
Dosing
The approved Barth-syndrome dose is 40 mg subcutaneously once daily in patients 30 kg and over, and trials used 4-40 mg daily. Community protocols typically sit at 5-10 mg because injection-site reactions scale sharply with dose and concentration.
Reconstitution calculator
Pre-loaded with SS-31’s vial size, water volume and typical dose. Change anything.
Typical: 10 mg · range 5–40
Draw to
50 u
0.5 mL · 10 mg
Concentration
20 mg/mL
200 mcg per unit
Doses per vial
1
Vial lasts
1 day
CheckThe draw fills more than 90% of the barrel. Workable, but there is no room for an air bubble or a correction.
Once mixed
Refrigerate at 2-8 C and use within 30 days; the peptide is relatively stable in solution but do not freeze it.
0.5 mL of bacteriostatic water into a 10 mg vial gives 20 mg/mL, so 10 mg is 0.5 mL (50 units); a 50 mg vial needs 2.5 mL for the same 20 mg/mL. Injection-site reactions are dose- and concentration-dependent — diluting further and rotating sites every day materially reduces them.
Storage
Before mixing
Refrigerated at 2-8 C the sealed powder is stable for around 24 months; keep it dry and out of light.
After mixing
Refrigerate at 2-8 C and use within 30 days; the peptide is relatively stable in solution but do not freeze it.
Reported benefits
- ▪Binds and stabilises cardiolipin in the inner mitochondrial membrane
- ▪Improves ATP output per unit oxygen in dysfunctional mitochondria
- ▪Reduces reactive oxygen species from electron leak rather than scavenging them afterwards
- ▪Improved muscle strength in Barth syndrome trials, the basis of its approval
- ▪Improved 6-minute walk distance in early mitochondrial myopathy studies
- ▪Best-evidenced compound in this category, with genuine phase 3 exposure data
Side effects
- ▪Injection-site reactions are the dominant adverse event — erythema, itching, induration and pain, common enough that trials tracked them as the primary tolerability issue
- ▪Some site reactions are severe or persistent enough to force dose reduction or stopping
- ▪Headache and dizziness
- ▪Nausea and gastrointestinal upset
- ▪Fatigue in the first week for some users
- ▪Occasional hypersensitivity-type rash beyond the injection site
Do not use if
- ▪Known hypersensitivity to elamipretide or to benzyl alcohol in bacteriostatic water
- ▪Renal impairment is not a labelled contraindication but requires dose reduction — adults with eGFR under 30 mL/min not on dialysis take 20 mg once daily instead of 40 mg, and there is no dosing guidance for dialysis patients. Roughly the entire dose is recovered in urine as elamipretide or its M1/M2 metabolites, and M1/M2 exposure rises up to 280% and 640% in severe impairment.
- ▪Pregnancy and breastfeeding — no human reproductive data
- ▪Broken, inflamed or previously reactive injection sites until fully healed
Evidence level — Human trials
Controlled human clinical data exists.
Approved by the FDA in September 2025 as Forzinity (elamipretide) for Barth syndrome; material sold as research-chemical SS-31 is not that approved product and is unapproved for any other use.
Commonly run with
MOTS-c
Mitochondrial-encoded peptide studied for insulin sensitivity and exercise capacity.
5 mg · 3x per week
Humanin
First mitochondrial-derived peptide discovered, studied for cytoprotection and metabolism.
1 mg · 3x per week
Epitalon
Pineal-derived tetrapeptide studied for telomerase activation and circadian regulation.
10 mg · Once daily during a course
SS-31 FAQ
If it is FDA-approved, is the research-chemical version the same thing?+
Chemically it is the same tetrapeptide, but the approved product is a sterile solution made to pharmaceutical standards with verified identity and purity. Research-chemical vials carry the usual risks of unverified content, endotoxin and mislabelled mass. Third-party testing is the only way to close that gap.
Why do the injection-site reactions happen and can I avoid them?+
SS-31 is strongly cationic, which irritates tissue at the depot site, and the reaction scales with dose and concentration. Diluting to a lower mg/mL, injecting at room temperature rather than straight from the fridge, and strict daily site rotation are the practical levers. For a minority the reactions persist regardless.
Will a healthy person notice anything?+
Often not much. The mechanism repairs efficiency in mitochondria that are already compromised, so the trial responses came from people with genuine mitochondrial disease. Older users and those with real fatigue pathology report more than young, healthy, well-trained ones.
Does it stack with MOTS-c?+
They act on different levers — SS-31 improves the efficiency of existing mitochondria, MOTS-c signals through AMPK toward metabolic adaptation — so they are not redundant. There is no interaction study, and no human data on the combination at all.
References
- 1.First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics — British Journal of Pharmacology (2014) PMID 24117165
- 2.Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy — Neurology (2018) PMID 29500292
- 3.A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism — Genetics in Medicine (2021) PMID 33077895
- 4.Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome — Orphanet Journal of Rare Diseases (2022) PMID 36056411
More longevity & mitochondrial
Epitalon
Pineal-derived tetrapeptide studied for telomerase activation and circadian regulation.
10 mg · Once daily during a course
Humanin
First mitochondrial-derived peptide discovered, studied for cytoprotection and metabolism.
1 mg · 3x per week
MOTS-c
Mitochondrial-encoded peptide studied for insulin sensitivity and exercise capacity.
5 mg · 3x per week