SS-31
Also known as Elamipretide, Bendavia, MTP-131, D-Arg-Dmt-Lys-Phe-NH2, Szeto-Schiller peptide 31
SS-31 is a four-amino-acid peptide that concentrates in the inner mitochondrial membrane and binds cardiolipin, stabilizing energy production. As elamipretide it has been through multiple human trials, most notably for the rare mitochondrial disease Barth syndrome.
Overview
SS-31 was designed in the early 2000s by Hazel Szeto and Peter Schiller while working on opioid peptides. They noticed that certain small peptides with alternating aromatic and basic residues accumulated in mitochondria at very high concentrations. SS-31 is one of those, built from D-arginine, a modified tyrosine, lysine, and phenylalanine. Its unnatural residues make it resistant to breakdown, and its charge pattern drives it to the inner mitochondrial membrane. Stealth BioTherapeutics licensed it and developed it as elamipretide.
It is unusual among research peptides in having a substantial human trial record. Elamipretide has been tested in heart failure, primary mitochondrial myopathy, dry age-related macular degeneration, and Barth syndrome, a rare genetic cardiolipin disorder. Results were mixed. The large mitochondrial myopathy trial missed its primary endpoint, while the small Barth syndrome program showed improvements in an open-label extension that were convincing enough that the FDA granted accelerated approval in 2025 under the brand name Forzinity after initially rejecting it. Macular degeneration results were encouraging in early phases and remain in development.
In animals SS-31 has an enormous literature: it protects the heart and kidneys from ischemia, reverses age-related decline in muscle energy production, improves mitochondrial function in old mice within hours, and reduces oxidative damage across many tissues. The community uses it as a general mitochondrial protectant and for endurance and aging, at doses well below the 40 mg daily used clinically. Gray-market SS-31 is not the pharmaceutical product and its purity varies.
How it works
SS-31 crosses cell membranes freely and concentrates over a thousandfold in the inner mitochondrial membrane, where it binds cardiolipin, a phospholipid unique to that membrane. Cardiolipin anchors the electron transport chain complexes and cytochrome c in the correct arrangement for efficient electron flow. When cardiolipin becomes oxidized or displaced under stress, electron transport gets leaky, ATP production falls, and reactive oxygen species rise. SS-31 binding stabilizes cardiolipin and the associated protein complexes, restoring the membrane curvature of the cristae, improving ATP output, and reducing electron leak. It also prevents cytochrome c from converting into a peroxidase that oxidizes cardiolipin and triggers apoptosis. Because it targets structure rather than scavenging radicals, it works differently from ordinary antioxidants.
What the research shows
- in vitroSS-31 binds cardiolipin and restores electron transport chain efficiency in ischemic mitochondria.
- rodentA single dose of SS-31 improved mitochondrial energetics and exercise tolerance in aged mice within one hour.
- rodentSS-31 reduced infarct size and kidney injury in rodent ischemia-reperfusion models.
- human RCTIn Barth syndrome, elamipretide improved six-minute walk distance and cardiac measures in an open-label extension after a negative crossover phase.
- human RCTIn the large primary mitochondrial myopathy trial, elamipretide did not beat placebo on the primary walking endpoint.
- clinical (approved drug)Elamipretide received FDA accelerated approval for Barth syndrome in 2025.
Evidence labels: rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
Dosing and protocol
Community protocols cluster around 5 to 10 mg daily. The clinical Barth syndrome dose is 40 mg subcutaneously once daily.
4-8 weeks, then reassess. Clinical use is continuous.
Any time; morning is common. Clinical dosing was once daily at a consistent time.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 10 mg | 1 mL | 10 mg/mL | 50 units |
| 30 mg | 2 mL | 15 mg/mL | 33.3 units |
| 50 mg | 3 mL | 16.667 mg/mL | 30 units |
Lyophilized: fridge or freezer, away from light. Reconstituted: fridge 2-8C, use within 4 weeks. SS-31 is more stable than most peptides because of its unnatural residues.
Cautions
- ▲Injection site reactions, including redness, itching, and small lumps, were the most common adverse event in trials.
- ▲The largest human trial was negative, so benefit in general mitochondrial fatigue is not established.
- ▲Research-grade SS-31 is not elamipretide and has no quality assurance behind it.
- ▲Community doses are a fraction of clinical doses, so effects people report may be placebo.
- ▲Long-term safety outside of clinical monitoring is unknown.
Commonly stacked with
Frequently asked
Is SS-31 the same as elamipretide?
Same molecule. Elamipretide is the drug name Stealth BioTherapeutics used in trials and for the approved product Forzinity. SS-31 is the original research code. What you buy from a peptide vendor is chemically meant to be the same but is not manufactured or tested to pharmaceutical standards.
Is it FDA approved?
As of 2025, yes, but narrowly. Elamipretide received accelerated approval for Barth syndrome, an extremely rare genetic disease, after a complete response letter earlier that year. It is not approved for aging, fatigue, or anything else, and the big trial in primary mitochondrial myopathy failed.
What dose do people use?
Community reports cluster around 5 to 10 mg daily by subcutaneous injection. Clinical trials used 40 mg daily subcutaneously or intravenous infusions. Nobody has shown the lower community doses do anything in humans.
Does it work as an antioxidant?
Not in the usual sense. It does not scavenge free radicals. It binds cardiolipin and physically stabilizes the mitochondrial inner membrane so the electron transport chain leaks fewer electrons in the first place. That is why it is described as a mitochondrial structural protectant.
References
- First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology, 2014
- The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology, 2013
- A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Genetics in Medicine, 2021
- Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology, 2023