Longevity and MitochondriaExtensively studiedmitochondrialcardiolipinelamipretideBarth syndromeheart

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.

Reviewed by the amino101 editorial team. , first published .

Status
Clinical-stage drug (elamipretide) with an FDA accelerated approval for Barth syndrome; research-grade SS-31 is not that product
Typical dose
5 to 40 mg
once daily
Route
Subcutaneous, Intravenous
Subcutaneous, abdomen or thigh, rotate sites since injection reactions are common
Cycle
4 to 8 weeks
Break: 2 to 4 weeks; clinical use is continuous
Storage
Fridge 2 to 8 C
fridge 2 to 8 C once mixed, use within 4 weeks; more stable than most peptides

Quick start

What people commonly do. Not a prescription.
Typical dose
5 to 10 mg
How often
once daily
Where
Subcutaneous, abdomen or thigh, rotate sites since injection reactions are common
Timing
any time, morning is common, keep it consistent day to day
Effects timeline
clinical endpoints were measured over weeks to months; community reports of better energy within 1 to 2 weeks are unverified
Storage
fridge 2 to 8 C once mixed, use within 4 weeks; more stable than most peptides
Cycle length
4 to 8 weeks
Break between
2 to 4 weeks; clinical use is continuous

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.

Molecular weight
639.8 Da
Length
4 amino acids
Type
Mitochondria-targeted tetrapeptide
Sequence
D-Arg-Dmt-Lys-Phe-NH2

Where the research stands

Human trials
Approved drug
Animal data
Extensive
Safety data
Established
Regulatory
FDA accelerated approval as elamipretide (Forzinity) for Barth syndrome, 2025; research-grade SS-31 is not that product
WADA
Not listed
Barth syndromeStrong evidence
  • Muscle strength and walking distance. TAZPOWER crossover RCT missed its primary endpoint, but the open-label extension showed sustained improvement in six-minute walk and cardiac measures, which supported accelerated approval.
Mitochondrial function in agingModerate evidence
  • Exercise tolerance in aged animals. Rodent study, a single dose improved muscle energetics and endurance in old mice within an hour.
  • Ischemia-reperfusion injury. Rodent models of heart attack and kidney injury showed smaller damage; the human EMBRACE STEMI trial was negative.
Dry age-related macular degenerationEmerging
  • Geographic atrophy. ReCLAIM-2 phase 2 RCT gave mixed results on vision with a signal on retinal structure; phase 3 ReNEW is ongoing.
Primary mitochondrial myopathyWeak or mixed
  • Walking endurance and fatigue. MMPOWER-3 phase 3 RCT did not beat placebo on the primary endpoint.
Heart failureWeak or mixed
  • Heart failure with reduced ejection fraction. PROGRESS-HF phase 2 RCT showed no meaningful improvement in cardiac function.
Key findings
  • 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.

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.

Levels over time

Modeled from the half-life. Illustrative, not measured.
Peak
about 30 minutes to 1 hour after subcutaneous injection
Half-life
Roughly 2 to 4 hours in plasma (clinical data)
Cleared
about 12 to 24 hours
Repeated dosing every 24 hDose
100%50%dose 16h12h18h24h
What this means for dosing

A half-life of 3 h against dosing every 24 h means each dose has cleared before the next. Nothing stacks; you start from zero every time, and the tissue effect is what carries over.

The peptide concentrates in the inner mitochondrial membrane far above plasma levels and stays there longer than the blood half-life suggests, which is why once-daily dosing was used in every clinical trial.

SS-31 dosage and protocols

Clinical use is continuous once-daily dosing with no cycling. Community protocols run 4 to 8 weeks then take a break, mostly out of caution and cost rather than evidence. No loading or tapering is used; the effect in animals appeared within hours of a single dose.

GoalDoseFrequencyRoute
Conservative community protocol5 mgonce dailySubcutaneous
Common community protocol10 mgonce dailySubcutaneous
Clinical trial range20 to 40 mgonce dailySubcutaneous
Approved Barth syndrome dose40 mgonce dailySubcutaneous
Timing

Food does not matter. Morning dosing is common and some people inject before training on the strength of the aged-mouse endurance data. Rotate sites every day since redness and lumps build up with repeated use of one spot. Often paired with MOTS-c on the same schedule.

Community protocols cluster around 5 to 10 mg daily. The clinical Barth syndrome dose is 40 mg subcutaneously once daily.

Dose calculator

U-100 insulin syringe
Draw
- units
- mL at -
- doses per vial. - per unit.

Units 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.

Common vial sizes and reconstitution
VialSuggested waterConcentrationLow dose draw
10 mg1 mL10 mg/mL50 units
30 mg2 mL15 mg/mL33.3 units
50 mg3 mL16.667 mg/mL30 units

How to reconstitute SS-31

  1. 1

    Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.

  2. 2

    Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.

  3. 3

    Draw the bacteriostatic water into a mixing syringe.

  4. 4

    Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.

  5. 5

    Swirl gently or leave it to dissolve. Do not shake.

  6. 6

    Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.

  7. 7

    Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.

  8. Full walkthrough with syringe reading and site rotation: reconstitution guide.
Quality check
  • ✓
    White, fluffy cake

    Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.

  • ✓
    Clear after mixing

    Once dissolved the solution should be water-clear with nothing floating in it.

  • !
    Slight clumping

    Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.

  • ✕
    Collapsed or melted

    Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.

  • ✕
    Cloudy or particles

    Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.

What to expect
  1. Week 1 to 2

    Injection site redness or itching is the most common thing people notice. Some report more energy or easier workouts, which trials did not confirm in healthy people.

  2. Week 2 to 4

    Reports of better exercise recovery and less fatigue; in trial populations any effect took months to show up on objective measures.

  3. Week 4 to 8

    Most healthy users notice little that is measurable; clinical benefit was specific to Barth syndrome, not general fatigue.

Interactions and stacking

MOTS-csynergistic

MOTS-c signals metabolic adaptation while SS-31 protects the machinery it acts on; complementary in theory, untested together.

NAD+compatible

NAD+ feeds the electron transport chain SS-31 stabilizes; a common mitochondrial pairing with no combined data.

Glutathionecompatible

Both reduce oxidative stress by different routes; no known conflict.

Semaglutidecompatible

Sometimes added during aggressive weight loss to support mitochondrial function; no data either way.

Prescription drugs in generalcompatible

Elamipretide is not metabolized by liver CYP enzymes and no drug interactions were flagged in trials, so it is one of the cleaner peptides to combine.

Other injectables at the same sitecaution

SS-31 injection reactions are common, and stacking a second injection in the same area makes irritation worse and harder to attribute.

Safety

Side effects and cautions
  • ▲Injection site redness, itching, swelling or small lumps
  • ▲Headache
  • ▲Dizziness
  • ▲Nausea
  • ▲Fatigue in some people, the opposite of what they expected
  • ▲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.
Stop and reassess if
  • ■Injection site reactions that spread, blister or leave persistent nodules
  • ■Hives, swelling or breathing trouble after a dose
  • ■No measurable benefit after 8 weeks; the largest human trial in general mitochondrial fatigue was negative
  • ■Feeling worse rather than better on it
Educational only. Dose ranges describe what appears in published research and community protocols. This is not medical advice and most of these compounds are not approved for human use. Talk to a clinician who knows your history.

Community poll

Self-reported by visitors. Not clinical evidence.
What is your experience with SS-31?
If you have used it, how well did it work for you?
Any side effects?
Where did you first hear about it?

SS-31: 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

  1. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology, 2014
  2. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology, 2013
  3. 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
  4. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology, 2023