Peptide Health Lab

Longevity & cellular

SS-31

Also known as: Elamipretide, MTP-131, Bendavia

Regulatory status
FDA approved
Evidence grade
Human RCT evidence

Last reviewed September 1, 2026 · 18 sources

What SS-31 is and how it works

SS-31 is a four-amino-acid peptide — D-Arg-dimethylTyr-Lys-Phe-amide — and the name is an index number from the Szeto–Schiller series developed at Weill Cornell. Its generic drug name is elamipretide; earlier in development it was called MTP-131 and, in the cardiology programme, Bendavia. Those are four names for one molecule. Other peptides in the same series are different molecules with their own data, and a result obtained with one of them is not a result for this one.[3]

The originating work described a class of cell-permeable peptides built on alternating aromatic and basic residues, with dimethyltyrosine supplying the radical-scavenging chemistry. In cultured neuronal cells and isolated mitochondria they concentrated roughly a thousandfold in the inner mitochondrial membrane, reduced reactive oxygen species, inhibited permeability transition and swelling, and prevented calcium-induced cytochrome c release; analogs lacking dimethyltyrosine did neither.[1]

The mechanism was pinned down more precisely later. Using a polarity-sensitive fluorescent analog, SS-31 was shown to bind with high affinity to cardiolipin, the anionic phospholipid of the inner mitochondrial membrane that cristae formation requires, and the SS-31–cardiolipin complex inhibited cytochrome c peroxidase activity. Pretreated rats undergoing renal ischemia retained cristae architecture and recovered ATP faster on reperfusion.[2] Structure-activity work across the tetrapeptide class later found that all the analogs tested bound cardiolipin-containing membranes but differed markedly in binding behaviour and in their effects on membrane surface charge, and that SS-31 was the one analog that did not adopt a compact reverse-turn conformation when membrane-bound.[3]

For a compound sold on a longevity story, that depth of biophysical characterization is rare. It is also, entirely, biophysics and preclinical pharmacology. What follows is what happened when the same molecule was asked to change an outcome in a person.

What the research actually shows

Primary mitochondrial myopathy — three randomized trials, ending in a failure. A phase 1/2 intravenous dose-escalation trial in 36 adults reported a mean 64.5 m gain on the six-minute walk test at the highest dose against 20.4 m on placebo, p=0.053, and the paper carries a Class I evidence classification that elamipretide improved that distance.[4] A 30-participant randomized subcutaneous crossover trial then missed its primary endpoint — a 19.8 m difference, P=0.0833 — while patient-reported fatigue measures reached significance, and injection-site reactions were reported in 80% of participants.[5] The pivotal phase 3 trial randomized 218 participants to 24 weeks of daily subcutaneous dosing or placebo and missed both co-primary endpoints: the six-minute walk difference was -3.2 m (p=0.69) and the fatigue score difference was -0.07 (p=0.37). That paper carries a Class I classification that elamipretide does not improve either outcome.[6] A subsequent post hoc genotype analysis of the same failed trial reported a benefit in patients with mtDNA-replisome variants, at p=0.06 on the walk test in that cohort, and the authors present it as the design basis for a further trial rather than as an established effect.[7]

Barth syndrome — the programme that produced the approval. A randomized, double-blind, placebo-controlled crossover trial in 12 subjects with this rare genetic disorder of cardiolipin metabolism reported, in the authors' own words, that in part 1 neither primary endpoint was met. The significant results — a 95.9 m six-minute walk gain and a 2.1-point symptom-score improvement at week 36 — came from the uncontrolled open-label extension that followed.[8] Ten patients entered that extension and eight reached week 168, with a cumulative 96.1 m walk-test improvement reported at that visit.[9] A separate retrospective study built a propensity-matched comparison of those eight treated patients against 19 untreated natural-history controls and reported differences of 79.7 m at week 64 and 91.0 m at week 76, plus dynamometry differences of 40.8 and 56.7 newtons.[10] An open-label extension and an external control are real evidence and they are not a randomized comparison.

Cardiology — one positive acute signal, two negative trials. In a randomized ascending-dose trial, a single four-hour intravenous infusion in patients with reduced ejection fraction produced significant reductions in left ventricular end-diastolic volume (-18 mL, P=0.009) and end-systolic volume (-14 mL, P=0.005) at the highest dose.[12] Twenty-eight days of daily subcutaneous dosing in 71 patients did not reproduce it: end-systolic volume did not differ from placebo in either dose arm, P=0.90 and P=0.28.[13] In a multicentre randomized phase 2a trial in first-time anterior ST-elevation myocardial infarction, a one-hour intravenous infusion did not reduce infarct size and was not associated with improvement in any prespecified imaging, angiographic, electrocardiographic, or clinical outcome.[11]

Ophthalmology — the same shape again, by two different routes. A 176-patient randomized, double-masked trial of daily subcutaneous dosing in dry age-related macular degeneration with geographic atrophy met neither co-primary endpoint; the ellipsoid-zone and letter-gain findings that the paper highlights carry P values the authors themselves label nominal.[14] A 12-patient randomized, vehicle-controlled trial of a 1% topical ophthalmic solution in Leber hereditary optic neuropathy met its safety primary and missed its efficacy primary: visual acuity in treated eyes was not significantly different from vehicle eyes at any time point.[15]

Older adults — the one study a longevity reader is actually looking for. In a randomized, double-blind, placebo-controlled trial, 39 healthy adults aged 60 to 85, enrolled because their mitochondria were functioning poorly, received a single two-hour intravenous infusion. Maximum mitochondrial ATP production rose against placebo immediately afterwards (ΔATPmax P=0.055, %ΔATPmax P=0.045), with no difference at day 7, no significant change in resting mitochondrial coupling, and no significant effect on volitional fatigue resistance.[16] In aged mice, by contrast, eight weeks of treatment reversed the age-related decline in ATP production and coupling and increased treadmill endurance — while mitochondrial protein expression was unchanged or reduced and respiration in permeabilized muscle fibres was no different from untreated aged animals.[17]

Where the evidence is weak

The primary endpoints, taken together, are the story. Across the trials described above, the randomized primary endpoints that were missed include both co-primaries of the phase 3 myopathy trial, both primaries of the Barth crossover phase, both co-primaries of the geographic-atrophy trial, the visual acuity primary in the optic-neuropathy trial, the infarct-size primary in the STEMI trial, and the ventricular-volume primary in the heart-failure trial.[6][8][14][15][11][13] A page that quoted only the favourable secondary and post hoc results from those same trials would be describing a different drug.

Mechanism is demonstrated; benefit is not. The clearest human result on this page is the one that separates the two. ATP production measurably rose after a single infusion in older adults, and fatigue resistance in the same muscle, in the same people, on the same day, did not change.[16] "It improves mitochondrial function" and "it makes a person function better" are two claims, and only the first has human support.

Nothing here was tested in a healthy adult over time. A PubMed search on 1 September 2026 combining elamipretide, SS-31 and MTP-131 with lifespan, longevity and life span, restricted to human studies, returned three records and every one of them was a narrative review rather than a trial; a parallel search combining the same compound terms with athletic performance, exercise performance, aerobic capacity and endurance in humans surfaced only the mitochondrial-myopathy trials already described above and two reviews. The one randomized study in people who did not have a diagnosed target disease administered a single infusion to adults aged 60 to 85 who were selected for impaired mitochondrial function, which is close to the opposite of a healthy-aging population, and it measured a biomarker rather than an outcome.[16] No published trial has given this molecule repeatedly to adults without a mitochondrial disease, and a 2026 sports-medicine review of approved and unapproved peptides marketed direct to patients covers it alongside compounds of both kinds while reporting that rigorous human safety data are scarce across the unapproved ones — a description that fits material labeled SS-31 that is not the approved prescription product rather than the approved product itself.[18]

A rare-disease dose has no bearing on a healthy adult. The 40 mg daily subcutaneous schedule that appears across the myopathy and Barth programmes was selected for people with a genetic mitochondrial disorder, and in the largest trial that used it the primary endpoints were still missed.[6]

The independence problem is real and it runs the wrong way for optimism. The clinical programme was sponsor-run, sponsor employees appear among the authors of several of the trial reports, and the human single-dose study in older adults was sponsor-funded with three authors who had been paid sponsor consultants.[16] Those disclosures are published and proper. They are also the reason to weigh this programme by its primary-endpoint results first and by the framing built around them second.

No confirmatory result has been published. A PubMed search on 1 September 2026 pairing the follow-on trial's name, NuPOWER, with elamipretide returned a single record — the post hoc analysis that proposes that trial — and no report of the trial itself.[7]

Legal and regulatory status

Elamipretide is an FDA-approved drug, and the approval is far narrower than the word usually suggests to a reader who arrived here from a longevity or performance framing. NDA 215244 was approved on 19 September 2025 to Stealth BioTherapeutics under the brand name FORZINITY, as an original new molecular entity reviewed under priority review with an orphan submission property, in a single dosage form: a subcutaneous solution, prescription only.

The approved indication is to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. It was granted under accelerated approval on the basis of an improvement in knee extensor muscle strength — an intermediate clinical endpoint — and the labeling states that continued approval for the indication may be contingent on verification and description of clinical benefit in a confirmatory trial. The labeled dosage for that indication is 40 mg subcutaneously once daily in patients weighing at least 30 kg, halved in adults with severe renal impairment; that is a description of a label, not guidance, and it applies to one rare genetic disease.

The approved labeling itself states that the drug was not superior to placebo on the primary endpoints of the randomized trial, which matches the published report of that trial's randomized phase.[8] There is no boxed warning. The labeling carries a contraindication for serious hypersensitivity with an explicit instruction not to rechallenge, warnings for hypersensitivity reactions and for benzyl alcohol toxicity in neonates, an injection-site reaction table in which every patient on drug reported erythema at the point of administration against a quarter of patients on placebo, and a note that increases in absolute eosinophil counts were seen frequently with administration of 30 days or longer.

Nothing about that approval extends to mitochondrial myopathy, heart failure, macular degeneration, optic neuropathy, aging, or athletic performance. Prescribing beyond an approved indication is a lawful exercise of a prescriber's judgment and it is also, by definition, prescribing into territory the approval never assessed. That gap is unusually wide here, because the territory outside this approval is not unexamined — it was examined in randomized trials, and those trials mostly came back negative.

Material labeled SS-31 or elamipretide that is not the approved prescription product carries none of this: no approved labeling, no assigned indication, no expiry date, and no regulated identity standard. Peptide Health Lab does not sell peptides and does not tell anyone where to obtain anything.

In tested sport, the 2026 World Anti-Doping Code International Standard Prohibited List — in force from 1 January 2026, retrieved from the World Anti-Doping Agency on 1 September 2026 via the United States Anti-Doping Agency's prohibited-list page — does not name elamipretide, SS-31, MTP-131 or Bendavia anywhere in its text. Its S0 non-approved-substances class, prohibited at all times, reaches any pharmacological substance not addressed elsewhere on the list that has no current approval by any governmental regulatory health authority for human therapeutic use; elamipretide has held an FDA approval since 19 September 2025, so on the face of that wording the clause does not reach this molecule. A PubMed search the same day combining elamipretide and SS-31 with doping, prohibited list and sports drug returned no records, so there is no indexed peer-reviewed statement of the position either. None of that is a clearance: the list is revised annually, classification decisions belong to the athlete's own governing body, and the list in force on the day of a test is the only one that governs it.

Questions to bring to a provider

The useful conversation is not "should I try SS-31." It is "here is the problem I actually have, and where does a drug approved for one rare genetic disease, whose trials in six other conditions mostly missed their primary endpoints, sit relative to it?" Questions worth raising:

  • What is the actual clinical question — fatigue, exercise intolerance, a cardiac finding, a vision change — and what has standard-of-care evidence behind it for that specific problem?
  • Given that the largest randomized trial in mitochondrial myopathy was Class I evidence of no benefit on walking distance or fatigue, what would have to be true for this to be worth considering outside its approved indication?[6]
  • Is there any reason to expect a different result in someone without a mitochondrial disease, when the one human study in older adults raised ATP production without changing fatigue resistance?[16]
  • What does an accelerated approval based on an intermediate endpoint actually establish, and what is the confirmatory trial supposed to answer?[8]
  • If a mitochondrial disorder is suspected, what genetic and functional workup comes before any drug conversation?
  • What would count as objective evidence that something changed — a timed walk, handheld dynamometry, imaging, a laboratory marker — and who would be doing the measuring?[10]

If the answer that comes back is that the randomized trials outside Barth syndrome mostly failed, that is not a clinician being dismissive. It is what the literature on this page says.

Evidence by claim

Grades describe how strong the evidence is; the line under each grade describes what kind of studies it is. How we grade evidence.

Muscle strength in Barth syndrome, the approved indication
Anecdotal reports only human RCT · human observational

In the randomized, double-blind, placebo-controlled crossover phase of the trial supporting this indication, neither primary endpoint was met in 12 subjects. Knee extensor strength was a secondary endpoint, and the increases appeared during the uncontrolled open-label extension rather than during the randomized phase; by week 168, eight patients remained. A separate retrospective study compared eight treated patients with 19 untreated natural-history controls using a propensity-score model and reported larger walk-test and dynamometry differences. The grade here is deliberately not the design grade of the parent trial: the positive strength signal comes from open-label and externally controlled data, not from the randomized comparison, and grading it as randomized evidence would credit the drug with a result the randomized phase did not produce.

[8] [9] [10]

Walking distance and fatigue in primary mitochondrial myopathy
Human RCT evidence human RCT

Three randomized placebo-controlled trials tested this directly and the programme did not succeed. A 36-participant phase 1/2 intravenous dose-escalation trial reported 64.5 m versus 20.4 m on the six-minute walk test at the highest dose (p=0.053), and the paper is labelled Class I evidence that elamipretide improved that distance. A 30-participant subcutaneous crossover trial missed its primary endpoint (19.8 m difference, P=0.0833) while several patient-reported fatigue measures reached significance. The pivotal 218-participant phase 3 trial missed both co-primary endpoints — six-minute walk test difference -3.2 m (p=0.69) and total fatigue score -0.07 (p=0.37) — and is labelled Class I evidence that elamipretide does not improve either at 24 weeks. A post hoc genotype analysis of that failed trial reported a benefit in a mtDNA-replisome subgroup that was itself only p=0.06 on the six-minute walk test, which the authors present as the basis for designing a further trial rather than as a demonstrated effect.

[4] [5] [6] [7]

Cardiac structure, function, and reperfusion injury
Human RCT evidence human RCT

In a multicentre randomized phase 2a trial in first-time anterior ST-elevation myocardial infarction, intravenous MTP-131 did not reduce the primary endpoint of infarct size by creatine kinase-MB area under the curve, and was not associated with improvement in any prespecified imaging, angiographic, electrocardiographic, or clinical outcome. In heart failure with reduced ejection fraction, a randomized ascending-dose trial of a single four-hour infusion reported significant reductions in left ventricular end-diastolic volume (-18 mL, P=0.009) and end-systolic volume (-14 mL, P=0.005) at the highest dose — a real positive acute signal. A later randomized trial of 28 days of daily subcutaneous dosing in 71 patients did not improve left ventricular end-systolic volume against placebo (P=0.90 and P=0.28 for the two dose arms).

[11] [12] [13]

Vision in dry age-related macular degeneration and in Leber hereditary optic neuropathy
Human RCT evidence human RCT

A 176-patient randomized, placebo-controlled, double-masked phase 2 trial of daily subcutaneous dosing in dry age-related macular degeneration with geographic atrophy did not meet either co-primary endpoint. The reported reductions in ellipsoid-zone attenuation and the letter-gain difference carry nominal P values that the authors themselves label nominal. In a 12-patient randomized, vehicle-controlled trial of a 1% topical ophthalmic solution in Leber hereditary optic neuropathy, the safety primary was met and the best-corrected visual acuity efficacy primary was not: the change from baseline in treated eyes was not significantly different from vehicle eyes at any time point, with the encouraging visual-field result coming from a post hoc analysis.

[14] [15]

Mitochondrial ATP production in older adult skeletal muscle
Human RCT evidence human RCT

In a randomized, double-blind, placebo-controlled trial, 39 healthy adults aged 60 to 85 who were enrolled on the basis of poorly functioning mitochondria received a single two-hour intravenous infusion. Maximum mitochondrial ATP production rose relative to placebo immediately after the infusion (ΔATPmax P=0.055, %ΔATPmax P=0.045). There was no difference at day 7, no significant change in resting mitochondrial coupling, and — despite the rise in ATPmax — no significant effect on volitional fatigue resistance. The study was sponsor-funded and three authors had previously been paid sponsor consultants. This is the single strongest piece of human evidence for the mechanism and it is also the clearest evidence that the mechanism did not translate into a functional result.

[16]

Healthy aging, physical performance, and lifespan
Animal studies only animal · review

In aged female mice, eight weeks of SS-31 reversed the age-related decline in maximum mitochondrial ATP production and in oxidative-phosphorylation coupling, restored glutathione redox status, and increased treadmill endurance — while mitochondrial protein expression was unchanged or reduced and respiration in permeabilized muscle fibres did not differ from untreated aged animals. That in-vivo versus ex-vivo discordance is part of the result, not a footnote. PubMed searches on 1 September 2026 pairing elamipretide, SS-31 and MTP-131 with lifespan, longevity and life span, and separately with athletic performance, exercise performance, aerobic capacity and endurance, restricted to human studies, returned only narrative reviews and the mitochondrial-myopathy trials described elsewhere on this page — so on the indexed record no published trial has measured a lifespan, healthspan, or athletic-performance outcome in people. A 2026 sports-medicine review of approved and unapproved peptides marketed direct to patients for musculoskeletal and performance purposes covers this molecule among both kinds and reports that rigorous human data are scarce across the unapproved compounds it surveys.

[17] [18]

Cardiolipin binding as the proposed mechanism
Animal studies only in vitro · animal

The mechanism is better characterized than for most compounds in this category. The originating work described a class of cell-permeable aromatic-cationic peptides that concentrate roughly a thousandfold in the inner mitochondrial membrane, reduce mitochondrial reactive oxygen species, inhibit permeability transition and swelling, and prevent cytochrome c release in isolated mitochondria and cultured neuronal cells. A later study used a fluorescent analog to show high-affinity binding to cardiolipin, showed that the complex inhibits cytochrome c peroxidase activity, and reported protection of cristae membranes in rats undergoing renal ischemia. Structure-activity work across the tetrapeptide series found that all four analogs tested bound cardiolipin-containing membranes but differed substantially in binding behaviour and membrane effects, and that SS-31 alone did not form the compact reverse-turn conformation the others adopted. The evidence is biophysical and preclinical; mechanism is not outcome.

[1] [2] [3]

Typical protocol range in the research

  • Adults with genetically confirmed primary mitochondrial myopathy, the pivotal phase 3 randomized placebo-controlled trial arm (n=109 on drug), as reported in the abstract

    40 mg per day subcutaneously for 24 weeks [6]

  • Adolescents and adults with genetically confirmed Barth syndrome, the randomized crossover trial arm (12 subjects) and the open-label extension that followed it, as reported in the abstracts

    40 mg per day subcutaneously, given for 12 weeks per crossover period and continued through a 168-week open-label extension [8] [9]

  • Healthy adults aged 60 to 85 enrolled on the basis of poorly functioning mitochondria, a single-dose intravenous study; the abstract describes the infusion duration but does not print a milligram or milligram-per-kilogram amount, so none is reproduced here

    A single two-hour intravenous infusion [16]

  • Adults with first-time anterior ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention, the intravenous phase 2a trial arm

    0.05 mg/kg/h infused over one hour [11]

  • Aged female mice (26 months at treatment start), the animal experiment that produced the exercise-tolerance result quoted in longevity contexts

    3 mg/kg/day for eight weeks [17]

Every entry above is a trial arm in a defined disease population, a single-dose study in older adults selected for impaired mitochondrial function, or a rodent schedule. None of them is a protocol for a healthy adult, and none is derived from approved labeling — the labeled dosage for the approved indication is described in the regulatory section instead, because it is a fact about a label rather than a finding in a paper. The routes are not interchangeable: intravenous infusion, daily subcutaneous injection, and topical ophthalmic solution were three different products in three different programmes.

Ranges are what published research reports, not a recommendation. PHL does not prescribe, and nothing here is personalized to you.

Side effects & safety signals

  • Injection-site reactions

    Reported in 80% of participants in a 30-person randomized crossover trial, the majority mild; described as the most common adverse event in the Barth syndrome open-label extension and among the most common events in a 176-patient randomized ophthalmic trial · Local rather than systemic in the published trials, and the most consistent tolerability finding across the whole subcutaneous programme. It is also the reason a reader should treat "well tolerated" as a statement about a monitored trial population rather than about open-ended use.

    [5] [9] [14]

  • Overall adverse-event burden higher than placebo

    86% of participants receiving elamipretide versus 71% receiving placebo in a 176-patient randomized ophthalmic trial · The difference was driven by injection-site events rather than by serious systemic toxicity in that trial. It is reported here because "well tolerated" is the phrase the trial reports use, and the underlying numbers are not the same as no adverse events.

    [14]

  • No established safety profile in healthy adults

    Not established · The only published randomized experience in people who did not have a diagnosed disease is a single two-hour intravenous infusion in 39 adults aged 60 to 85 who were enrolled specifically because their mitochondria were functioning poorly. A 2026 sports-medicine review of approved and unapproved peptides marketed direct to patients covers this molecule among both kinds and reports that rigorous human safety data are scarce across the unapproved compounds it surveys — a description that fits material labeled SS-31 that is not the approved prescription product, not the approved product itself. Absence of an adverse-event record in healthy adults is an absence of data, not a finding of safety.

    [16] [18]

  • Long-term exposure characterized only in a very small cohort

    Not quantified beyond the trial populations · The longest published continuous exposure is a 168-week open-label extension in which eight patients with a rare genetic disease reached the final visit. The largest randomized exposure ran 24 weeks in 109 people on drug. Nothing in the published record describes multi-year exposure at any scale, in any population, or in anyone without a mitochondrial disease.

    [9] [6]

  • Intravenous tolerability does not transfer to daily subcutaneous use

    Not applicable across routes · In the intravenous programme, a one-hour infusion in patients undergoing coronary intervention and a single four-hour ascending-dose infusion in heart failure were both reported as safe and well tolerated, with blood pressure and heart rate stable and no serious adverse events. Those are findings about one or two infusions under direct monitoring, and they say nothing about daily subcutaneous dosing over months.

    [11] [12]

Published lists are never exhaustive, so report anything unexpected to a licensed provider.

Storage, handling & reconstitution

Lyophilized storage
The approved elamipretide product is not a lyophilized powder at all. It is supplied as a ready-to-use sterile aqueous solution in single-patient-use vials, manufactured under a real stability programme with an assigned expiry date, and the approved labeling directs refrigerated storage between 2 °C and 8 °C without freezing. That labeling is dispensed with the prescription and is the only stability information about this molecule that has a manufacturer standing behind it.
Reconstituted storage
Because the approved presentation is already in solution, the relevant labeled window is an in-use one rather than a post-mixing one: after the first dose is withdrawn, the labeling permits the opened vial to be held either refrigerated or at controlled room temperature, and assigns a discard date measured in days rather than weeks. The dispensed labeling states the window for the vial in hand.
Reconstitution
Not applicable. The approved elamipretide product is supplied as a ready-to-use aqueous solution for subcutaneous injection rather than as a freeze-dried powder, so there is nothing to reconstitute and no diluent question to answer.
Handling notes
Because elamipretide is an approved drug, an expiry date, a labeled in-use period, and a manufacturer stability programme exist for it — a categorical difference from the unapproved compounds elsewhere in this library. None of that transfers to material labeled SS-31 that is not the approved product: such material has no assigned expiry, no lot-level stability testing, and no regulated identity behind its label.

The how-to guides cover the conventions behind these fields, and what the published stability data does and does not establish: Storage, Reconstitution, Handling.

Questions for your provider

Bring this page to a licensed provider. A provider can order labs, review your medications and history, and tell you whether anything here is relevant to your situation. This page can't. Peptide Health Lab does not prescribe and does not sell peptides.

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Citations

18 sources · every identifier checked against PubMed

Before you act on any of this

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