Skip to content
PeptideHound

Protocols

SS-31 protocols in the published literature

StatusFDA approved · limited indication

PeptideHound Staff · Last editorially reviewed · 17 sources

SS-31 (elamipretide) has one approval, and it is narrow: in 2025 elamipretide became the first disease-specific treatment approved for Barth syndrome, a rare inherited disease. Outside that one label nothing about it can honestly be called a correct amount, only protocols written for trials in rare mitochondrial disease, heart failure and eye disease.

What exists instead is a drug-development record: a decade of registered trials, each carrying a protocol written for that trial and for nobody else. One figure repeats across the published human work, and it is 40 mg a day, injected under the skin. In the phase 3 MMPOWER-3 trial, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. In a separate Barth syndrome study, patients entering the open-label extension continued elamipretide 40 mg subcutaneous daily for a further 168 weeks.

Read where those two numbers come from. Both are trial protocols for named inherited diseases, run under supervision with material of known identity, and the larger of the two did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score. That trial is now listed as TERMINATED on the public registry. A protocol that was tried and did not work is still a protocol, and it was never designed to establish a suitable amount for a healthy person.

The approval covers elamipretide as an approved product in Barth syndrome. It does not transfer to material sold as SS-31, or to any other use or population. Material sold under the SS-31 name carries no approved strength and no established schedule, and no study among the research behind this page has measured what is inside any particular vial of it.

Evidence: Not dosing guidance · every figure below is a parameter from a registered trial or an animal experiment · the one repeated human figure is 40 mg a day under the skin, in two rare inherited diseases · no dose-finding study in a healthy population has been published

human RCT

There is no recommended amount for SS-31, and that is a fact about the regulatory record rather than a dodge. Elamipretide has a single approval, and its wording is narrow: elamipretide is indicated for the improvement of muscle strength in individuals with Barth syndrome17. That approval covers elamipretide as an approved product in that one disease. It does not transfer to material sold as SS-31, or to any other use or population, and none of the sources cited on this page reproduces the amount on that label. Outside it, what exists is a decade of registered trials in rare inherited disease. One figure keeps coming back, and it is 40 mg a day, under the skin. In the phase 3 MMPOWER-3 trial, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously.1 In the Barth syndrome work that followed, patients entering the open-label extension continued elamipretide 40 mg subcutaneous daily.2 Both of those are trial protocols, each written by investigators for one supervised group of patients, using material of known identity and strength. Reporting a protocol is not the same act as handing somebody a schedule, and neither trial set out to establish a suitable amount for anybody outside it.

What is actually on an SS-31 peptide dosage chart?

human RCT

Charts circulating under this name usually show a ladder of weekly amounts with a cycle length printed beside them, arranged as though a single sequence applied to everyone. The published record holds nothing of that shape at all. What it holds is two daily figures from two trials in two unrelated inherited conditions. MMPOWER-3 randomised 218 adults, 109 to elamipretide and 109 to placebo, in primary mitochondrial myopathy, a group of genetic disorders that impair mitochondrial oxidative phosphorylation, which is the process cells use to turn fuel into usable energy.1 The Barth syndrome work was a 28-week randomized, double-blind, and placebo-controlled trial followed by a 168-week open-label extension.2 An honest chart built from those two lines would carry two rows, each labelled with the rare disease it came from. Anything longer has been assembled from somewhere other than the published trial record. A figure that no study covered here supports tells a reader about whoever typed it rather than about the compound, and it cannot be checked against anything.

How much SS-31 was given per day?

human RCT

Per day is the right unit for the published human work, because both trials that report an amount gave it once daily rather than weekly. One ran 40 mg a day for 24 weeks against placebo, and the extension study continued the same 40 mg daily for a further 168 weeks.12 Whether a larger amount would do more has been examined once, indirectly, and the signal was faint. A later analysis of the same trial showed a weak positive correlation between plasma elamipretide concentration and 6MWT improvement, where the 6MWT is a six-minute walking test used as a measure of exercise capacity.3 Read the weight of that carefully. The parent trial did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score, the two things it was built to measure.1 A correlation found inside a subgroup of a trial that missed its own endpoints is a reason to be careful with the number rather than a reason to raise it.

Amounts of elamipretide in the two human trials described above that report one. Amounts studied in people with rare diseases, not a dosing guide.
StudyAmountHow oftenLength
Placebo-controlled trial40 mgOnce daily24 weeks
Extension study40 mgOnce dailyA further 168 weeks

How was SS-31 administered, and by what route?

human RCT

Under the skin, in every human trial that reports an amount, and the choice of route was not a free one. A 2023 study in mice notes that elamipretide is a short tetrameric peptide that is not orally bioavailable, limiting its routes of administration.5 In plain terms, swallowing it does not work. The registered trials then split by target organ. One phase 1 study gave Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration, an eye disease of ageing.10 A separate line of eye work used an Elamipretide Topical Ophthalmic Solution instead, which is to say eye drops rather than a needle.11 The heart work took place on a hospital ward. Blood was obtained from patients (n=19) after a first heart attack, and 10 of the patients received the mitochondria-targeting peptide elamipretide.4 No trial among the research behind this page has compared one route against another, so the registered record shows which routes were used rather than which one delivers more of the compound where it is intended to act.

How long did people stay on SS-31 in the trials?

human RCT

Two published answers exist and they are a long way apart. The myopathy trial ran 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously, which is a little under six months of daily injections.1 The Barth syndrome work ran far longer, through a 168-week open-label extension in which everyone involved knew they were receiving the compound.2 Ten patients entered the OLE; 8 reached the week 168 visit, so the longest human exposure on record rests on eight people with an inherited disorder of heart and muscle, none of them blinded to what they were taking.2 How quickly anything changes is a separate question, and neither trial was built to answer it. Both assessed participants at fixed visits, so they report where a group stood at week 24 or week 168 rather than the week in which a difference first appeared. Anyone quoting a time to effect for this compound is quoting something the published schedule of assessments cannot show.

What amounts were used in the heart studies?

human RCT

The heart trials are where the largest exposures are described, and they are also the place where the published numbers stop. A 2022 review states that in early-phase clinical trials, elamipretide administration has not resulted in any severe adverse events.6 The same sentence adds that the gains in blood flow through the heart came at highest doses.6 That phrase is as close to a figure as the sentence gets. The registered study behind it looked at the Cardiac and Renal Effects of Short Term Treatment With Elamipretide, and its entry lists no amount at all.12 The earlier heart-attack work is smaller still, and it reported a blood marker rather than a schedule. In that study elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction in the ten treated patients.4 One hospital admission, a single blood marker, and no amount anywhere in the published report is the whole of what is available.

Is there an amount for performance, bodybuilding or healthy ageing?

registered trial

Not in people, and the gap is worth stating precisely. The published work on exercise capacity in ageing is entirely in animals, and it is specific about frequency while staying silent on quantity. A 2023 study tested whether twice weekly intermittent injections of elamipretide could match the same gains as continuous long-term infusion.5 It ran for eight months, which is a large slice of a mouse life. The authors found that intermittent treatment with elamipretide for 8 months preserved exercise tolerance and left ventricular mass in mice.5 Kidney function did not follow, as it had under the continuous schedule.5 Notice what was actually being compared: two injection schedules set against each other in aged female mice, rather than an amount against a person. The experiment names a frequency and a duration and no quantity at all, so there is no figure inside it that could be carried anywhere. A phase 2 Study of Healthy Aging and Physical Function With Elamipretide is listed as RECRUITING and has published nothing.15

Is SS-31 cycled, and is there an off period?

human RCT

No trial among the research behind this page has tested a break, a taper or a repeat course, so there is no cycle length available to report. What the record contains instead is uninterrupted daily administration for as long as each trial lasted, which was 24 weeks in the myopathy study and a further 168 weeks in the extension that followed the Barth syndrome trial.12 The nearest anyone has come to a cycling question was asked in mice, and it was asked about frequency rather than about stopping. The ageing study compared twice weekly intermittent injections of elamipretide against continuous long-term infusion over eight months.5 That is a comparison between two uninterrupted schedules rather than between using something and pausing it. No study among the research behind this page has published what happens when a course ends, whether anything persists, fades or rebounds, which means the cycling question has not been asked rather than answered and found wanting.

How long should SS-31 be taken before MOTS-c?

human RCT

No study among the research behind this page has given SS-31 and MOTS-c together in any order, at any interval, in any species. There is no sequencing information because there is no combination information, and the two compounds have never appeared inside the same published protocol. What can be said is what each record separately contains. In MMPOWER-3 the only comparison was elamipretide against placebo, with no second compound in either arm of the trial.1 That isolation is the point of the design, because a second compound arriving on a schedule of its own would make any result impossible to attribute. So the question is being put to a literature that never addressed it, and the honest answer is a description of that silence rather than a number of weeks. Our comparison page sets out what each of the two compounds has actually been studied for, which is a different question from the order anybody might use them in.

How much bacteriostatic water goes into a 10 mg vial of SS-31?

human RCT

That is arithmetic, and it is one of the few questions on this page with a definite answer. A 10 mg vial holds 10,000 micrograms whatever volume is added to it, and the diluent only decides the concentration that results. One millilitre of bacteriostatic water produces 10,000 mcg/mL, two millilitres produces 5,000 mcg/mL, and five millilitres produces 2,000 mcg/mL. On a U-100 insulin syringe every unit mark is one hundredth of a millilitre, so at 5,000 mcg/mL a single mark holds 50 micrograms and ten marks hold 500 micrograms. Those are conversions between units and they hold whatever anybody decides to draw. What the arithmetic cannot supply is the figure to aim at, and the scale of the published trials makes that point sharply. Participants received elamipretide at a dose of 40 mg/d or placebo subcutaneously, which is four times the entire contents of a 10 mg vial every single day, under supervision, for a diagnosed inherited disease.1

How do mg, mcg and syringe units line up?

human RCT

One milligram is a thousand micrograms, so a 10 mg vial holds 10,000 mcg and a 50 mg vial holds 50,000 mcg. Milligrams measure the compound itself while millilitres measure the liquid it has been dissolved in, and the two quantities are unrelated until a diluent volume has been chosen. Concentration is the bridge between them: the total micrograms divided by the millilitres of diluent gives micrograms per millilitre. A U-100 insulin syringe is marked in units rather than in volume, and since one hundred units make a millilitre, each mark carries a hundredth of a millilitre of whatever concentration was mixed. The published trial figures arrive in milligrams per day rather than in syringe units, so moving between the two is arithmetic rather than interpretation.1 Our reconstitution and conversion tools will run these sums on the numbers you enter, and neither of them proposes a target amount, because no established target exists to propose.

Why is there still no established amount after a decade of trials?

human RCT

An amount becomes established when a regulator approves a product at that amount for a stated indication, and that has happened once, for one disease. In 2025 elamipretide became the first disease-specific treatment approved for Barth syndrome.16 That label belongs to the approved product in that disease and establishes nothing for SS-31 bought elsewhere or for anyone else. The largest trial in the programme, registered as a study of the Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy, now carries the status TERMINATED on the public registry.9 Its own conclusion is blunt. The trial provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks compared with placebo in patients with primary mitochondrial myopathy.1 A later analysis of the same participants found a signal in one genetic subgroup. Those data serve as the foundation for a follow-up Phase 3 clinical trial in patients who share that profile.3 That is how a development programme continues after a negative result, and it is also why the one repeated human figure on this page is still 40 mg a day, taken from trial protocols rather than from the Barth syndrome label.

Why do the published amounts and routes vary?

registered trial

They vary considerably less than the circulating charts imply, and where they do differ it tracks the organ under investigation rather than any hunt for an optimum. The muscle trial and the Barth syndrome extension both landed on 40 mg daily under the skin, which is the same number twice in two unrelated diseases. The eye programme is where the real variation lives, and it is a variation of route. One study ran an Elamipretide Topical Ophthalmic Solution in Fuchs' Corneal Endothelial Dystrophy (FCED), a disorder of the cornea.14 A separate phase 3 study used Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration.13 A 2025 review of eye delivery lists elamipretide among approaches that have achieved FDA approval within the past five years or have advanced to Phase 3 development, and in eye disease it is the second.7 So the spread follows disease and route rather than any search for an optimum. No dose-finding study has been published in people without one of these diagnoses. That is the study that would have to exist before any of these figures meant much outside the illness it was tested in.

What we don’t know

The gaps in the evidence matter as much as the findings.

  1. 01Any amount for a person without one of these rare diagnoses. The only repeated human figure comes from two trials in inherited mitochondrial and cardiac disease, and no dose-finding work has been published outside them.
  2. 02Whether more or less than 40 mg a day changes anything. The single analysis that looked found only a weak correlation between blood concentration and walking distance, inside a subgroup of a trial that missed its endpoints.
  3. 03What a course shorter than 24 weeks does. Both published trials assessed people at fixed visits months apart, so nothing describes the first weeks.
  4. 04Whether cycling, tapering or repeating a course matters. No trial among the research behind this page has tested a break of any length in any species.
  5. 05How the mouse schedules would translate. The ageing work reports twice-weekly injections over eight months and names no quantity at all, so there is no figure in it to scale.
  6. 06Whether one route outperforms another. Injection under the skin, eye drops and hospital administration all appear in the registered programme, and none has been compared against another.
  7. 07What is in material sold under the SS-31 name. No analysis among the research behind this page has measured the identity, strength or sterility of anything outside the trial supply.
  8. 08How long anything lasts after the last injection. The longest published exposure ends at week 168 and nothing follows the eight people who reached it.

Sources

  1. 1Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial Neurology 2023. doi:10.1212/WNL.0000000000207402human RCT
  2. 2Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER Genet Med 2024. doi:10.1016/j.gim.2024.101138human RCT
  3. 3Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial Orphanet J Rare Dis 2024. doi:10.1186/s13023-024-03421-5human RCT
  4. 4The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction Eur Heart J Acute Cardiovasc Care 2019. doi:10.1177/2048872617710789human RCT
  5. 5Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice Geroscience 2023. doi:10.1007/s11357-023-00754-0animal model
  6. 6Targeting mitochondrial dysfunction with elamipretide Heart Fail Rev 2022. doi:10.1007/s10741-021-10199-2review
  7. 7Beyond the injection: delivery systems reshaping retinal disease management Expert Opin Pharmacother 2025. doi:10.1080/14656566.2025.2496424review
  8. 8Energy-replenishing, mitochondria-targeted hydrogel microspheres mitigate sarcopenia via cellular senescence amelioration J Control Release 2026. doi:10.1016/j.jconrel.2025.114595human pilot / early trial
  9. 9A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension NCT03323749registered trial
  10. 10An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration NCT02848313registered trial
  11. 11A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for Treatment of Leber's Hereditary Optic Neuropathy NCT02693119registered trial
  12. 12A Phase 2 Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment With Elamipretide in Patients Hospitalized With Congestion Due to Heart Failure NCT02914665registered trial
  13. 13ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD) NCT06373731registered trial
  14. 14A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for the Treatment of Fuchs' Corneal Endothelial Dystrophy (FCED) NCT02653391registered trial
  15. 15Study of Healthy Aging and Physical Function With Elamipretide NCT07275424registered trial
  16. 162025 FDA TIDES (Peptides and Oligonucleotides) Harvest Pharmaceuticals (Basel) 2026. doi:10.3390/ph19020244review
  17. 17Barth Syndrome GeneReviews 1993. PMID 25299040review