SS-31 (Elamipretide): What It Is, Where to Get It Prescribed, and What It Costs

SS-31 is a tetrapeptide — four amino acids in an alternating aromatic and cationic pattern. That pattern lets it cross cell membranes freely and concentrate on the inner mitochondrial membrane without a transporter and without depending on the mitochondrion's membrane potential, so it still reaches mitochondria that are in trouble.

Once there it binds a single lipid, cardiolipin, found almost exclusively in the inner mitochondrial membrane, where it holds the membrane's folds (the cristae) in shape and organises the respiratory complexes for efficient electron transport. The 2014 review in the British Journal of Pharmacology that describes its discovery calls it a cardiolipin-protective compound. That is the whole of the mechanism, and it is more specific than most peptides can claim.

The compound was developed by Hazel Szeto and Peter Schiller, so the research literature calls it SS-31; its development code was MTP-131; its generic drug name is elamipretide, and in September 2025 the FDA approved a branded version, Forzinity, for one rare genetic disease. All three names are the same molecule. What differs between a paper and a label is the dose, the formulation and the population studied, which is covered below.

It is not a hormone, a growth hormone secretagogue or a metabolic signal in the way MOTS-c is, and it does not move anything on a standard blood panel. It is not a general antioxidant — the research describes it preventing one kind of reactive oxygen at one site. And it is not an approved treatment for ageing, fatigue, athletic performance or "mitochondrial health" in people without a mitochondrial disease. Those uses are an extrapolation from the disease work, and this page says so plainly.

The foundational finding, in the Journal of the American Society of Nephrology in 2013, used a fluorescent analogue of the peptide to show high-affinity binding to cardiolipin. In rat kidneys subjected to ischaemia, pre-treatment protected the cristae from collapsing and prevented mitochondrial swelling. Cristae are where ATP is made; if their structure goes, so does the capacity to make energy, however much fuel is available.

Cytochrome c normally carries electrons along the respiratory chain. When it binds oxidised cardiolipin it starts acting as a peroxidase, oxidising the lipid it sits on in a self-reinforcing loop that damages the membrane. The 2013 work reports that the SS-31–cardiolipin complex inhibits that peroxidase activity while leaving the electron-carrying role intact. This is the specific sense in which SS-31 "reduces reactive oxygen species": preventing one source rather than mopping up afterwards.

With the cristae protected, the same animal work reports much faster recovery of ATP once blood flow returns. The 2014 review extends this to the broader claim that a cardiolipin-protective compound can restore bioenergetics across conditions that share energy failure. That claim is the theoretical basis for every off-label use; whether it holds in a given human population is what the trials tested.

Barth syndrome is caused by variants in TAZ, whose product remodels cardiolipin into its mature form; affected individuals accumulate monolysocardiolipin relative to cardiolipin, and that MLCL/CL ratio is the diagnostic biomarker. The 168-week open-label extension of the Barth syndrome trial, in Genetics in Medicine in 2024, reports the ratio improving on treatment and correlating with clinical outcomes — the one human population where a mitochondrial biomarker was tracked alongside function.

TAZPOWER, in Genetics in Medicine in 2021, was a randomised, double-blind, placebo-controlled crossover in twelve males aged 12 to 35 with genetically confirmed Barth syndrome: 40 mg daily or placebo for 12 weeks, a washout, then the opposite. Neither primary endpoint — the six-minute walk test and the Barth Syndrome Symptom Assessment — was met in the randomised part.

Ten participants continued open-label on 40 mg daily. At 36 weeks the paper reports a 95.9-metre gain in walk distance (p = 0.024), a 2.1-point symptom improvement (p = 0.031), and improvements in knee extensor strength and some cardiac parameters. The 168-week results, in 2024, report the walk gain sustained (96.1 metres, p = 0.003), fatigue scores below baseline at every visit, and improved left ventricular volumes. Eight of ten reached the final visit.

The FDA's accelerated approval rested on knee extensor strength as an intermediate endpoint, not on the failed primaries. A confirmatory trial is a condition of approval and is running now.

The largest programme and the clearest negative result.

A five-day intravenous study in Neurology in 2018 (36 adults) reported a dose-dependent walk-distance signal that fell just short of significance (p = 0.053). MMPOWER-2, in the Journal of Cachexia, Sarcopenia and Muscle in 2020, was a 30-person crossover of 40 mg daily for four weeks: a 19.8-metre walk difference that did not reach significance (p = 0.083), a patient-reported fatigue improvement that did (p = 0.0006), and injection-site reactions in 80 per cent.

MMPOWER-3, in Neurology in 2023, was the pivotal phase 3: 218 participants on 40 mg daily or placebo for 24 weeks. It did not meet either primary endpoint. The walk-distance difference was −3.2 metres (p = 0.69) and the fatigue-score difference −0.07 (p = 0.37). The authors classify it as Class I evidence that elamipretide does not improve walking distance or fatigue at 24 weeks in this population.

A post hoc analysis in Orphanet Journal of Rare Diseases in 2024 found the subgroup with nuclear-DNA replisome variants (mostly POLG and TWNK) trended toward benefit (p = 0.06). That is hypothesis-generating by definition and is the basis for a further trial in that narrower group; it does not rescue the main result.

PROGRESS-HF, in the Journal of Cardiac Failure in 2020, randomised 71 patients with reduced-ejection-fraction heart failure to placebo, 4 mg or 40 mg daily for 28 days. The primary endpoint, change in left ventricular end-systolic volume on cardiac MRI, was not different from placebo at either dose, nor was ejection fraction. Adverse event rates were similar across groups.

ReCLAIM-2, in Ophthalmology Science in 2024, randomised 176 patients with dry AMD and non-central geographic atrophy 2:1 to 40 mg daily or placebo for 48 weeks. It did not meet its primary endpoints (low-luminance visual acuity and atrophy area). On a pre-specified secondary measure, treatment was associated with a 43 per cent reduction in progression of complete ellipsoid-zone loss (nominal p = 0.0034), and more patients gained ten or more letters of low-luminance acuity (14.6 versus 2.1 per cent). The company's phase 3 eye programme is built on that endpoint.

Elamipretide has been studied in randomised, double-blind, placebo-controlled trials in four diseases, at 40 mg subcutaneously daily, for four to 48 weeks, with open-label follow-up to 168 weeks in Barth syndrome. The randomised primary endpoints were missed in every indication. The positive findings are the sustained open-label improvements in Barth syndrome including the strength result behind the accelerated approval, a fatigue signal in the short myopathy crossover, a genotype subgroup in the phase 3, and a photoreceptor-preservation secondary endpoint in AMD.

There are no randomised human trials of elamipretide in healthy adults, in age-related fatigue, in athletic performance or in any wellness or longevity indication. The compounded vial on this page is prescribed for uses the trials did not test, at a dose the trials did not use.

• It does not establish benefit in people without a mitochondrial disease.
• It does not establish that the compounded dose does what the trial dose did. The trials used 40 mg daily; the directions here deliver 0.25 mL of a 2 mg/mL solution, a small fraction of that even at the higher strength.
• It does not establish an effect on walking distance or fatigue in the largest population studied. MMPOWER-3 is a clean negative on those endpoints.
• It does not establish an effect size or timeline for any off-label use. What prescribers describe is clinical experience.
• It does not establish long-term safety in healthy adults.

In MMPOWER-2, four weeks of the full trial dose produced a fatigue improvement and a walking-distance change that did not reach significance. At a compounded dose, prescribers generally describe the first vial as a tolerability period: injection-site reactions settling and subjective energy either changing or not. Noticing nothing in the first month is common and is not evidence either way.

If the mechanism is doing anything in a given person, this is where prescribers describe subjective reports clustering — steadier energy through the day, less post-exertional fatigue. Nobody has measured this in healthy adults, and subjective energy is the outcome most susceptible to expectation.

The Barth syndrome extension is the only long-duration human data; its gains accrued over 36 weeks and held to 168 weeks, at the full dose, in a population that does not resemble most people reading this page. That should temper any expectation of a fast response.

No withdrawal, rebound or dependency is described anywhere in the literature. The peptide is cleared within hours. Whether any subjective change persists is the same open question that applies to stopping any mitochondrial intervention.

The directions are written in millilitres and insulin-syringe units because that is what you can read off the barrel. 0.25 mL is 25 units on a U-100 syringe. You are not calculating anything — the number is printed on your medication.

Subcutaneous means into the fat layer, not the muscle. Abdomen and outer thigh are the usual sites, rotated. Mornings, because energy-related subjective effects are easier to judge across a day. Monday through Friday rather than daily is a prescriber convention that rests the injection sites; the trials all dosed every day.

Twenty doses at five per week is four weeks, which is why refills run on a 28-day cycle. One vial per fill, always — not a stockpile. The compounded vial is multi-dose; the approved product's single-patient vial is discarded eight days after opening, one of several practical differences between the two.

Refrigerated, and it ships that way in insulated packaging with ice packs. Beyond-use dating runs from first puncture and is printed on the label; the pharmacy's dating governs, not the molecule's reputation for stability.

Both get called "mitochondrial peptides," which hides how different they are. SS-31 is a synthetic tetrapeptide that binds a lipid in the inner membrane and is described as protecting the machinery that makes ATP. MOTS-c is encoded by the mitochondrial genome and is described as a signal that travels to the nucleus and regulates metabolic genes. SS-31 has a substantial human trial programme; MOTS-c does not.

NAD+ is a substrate: it supplies a coenzyme the respiratory chain consumes. SS-31 supplies nothing; it is described as protecting the structure in which that coenzyme is used. Different bottlenecks; some prescribers use them together, though no trial has tested the combination.

Same molecule, different products. Forzinity is approved, 80 mg/mL, 40 mg daily, for Barth syndrome, with a label and a confirmatory trial. The compounded vial is 2 mg/mL or 10 mg/mL, dosed at 0.25 mL by the directions above, prepared to your prescription, and not approved. If you have Barth syndrome, the approved product through a specialist is the right path. For any other use, neither is approved.