A mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane. The FDA approved it in September 2025 as FORZINITY, to improve muscle strength in Barth syndrome [8][9]; phase 3 trials in primary mitochondrial myopathy and in dry age-related macular degeneration missed their primary endpoints [13][14].
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team · Editorial standards
Subcutaneous
Route
3 recommended
Sites
Once daily
Frequency
Preparation
Nothing, for the approved product — FORZINITY is supplied as a ready-to-use 80 mg/mL solution and is not reconstituted [8]
The steps below apply only to research-grade lyophilised SS-31, which has no approved label behind it
Bacteriostatic water
Insulin syringes (29-31 gauge)
Alcohol swabs
Pro tip
Prepare all supplies on a clean surface before you begin. Having everything ready makes the process smoother and more sterile.
Mixing
Wash your hands thoroughly with soap and water. Gather all supplies on a clean, flat surface.
Remove the plastic cap from the peptide vial and wipe the rubber stopper with an alcohol swab. Let it air dry.
Draw the appropriate amount of bacteriostatic water into a sterile syringe.
Insert the needle into the vial at an angle, aiming at the inside wall of the vial. Slowly push the plunger to let the water trickle down the glass wall -- do NOT squirt directly onto the powder.
Once all water is added, gently swirl the vial in a slow circular motion. Never shake the vial, as this can damage the peptide bonds.
Continue swirling until the powder is completely dissolved and the solution is clear. If particles remain, let the vial sit for a few minutes and swirl again.
Label the vial with the date of reconstitution, the peptide name, and the concentration (e.g. 250mcg per 0.1mL).
Example calculation
FORZINITY needs no calculation: the vial holds 80 mg/mL, so a 40 mg dose is 0.5 mL [8]. For research-grade lyophilised powder, a 50 mg vial reconstituted with 2.5 mL of bacteriostatic water gives 20 mg/mL, so 2 mL (200 units on an insulin syringe) is the 40 mg dose.
Dose calculation
The dose is 40 mg once daily in both cases [8]. From the 80 mg/mL approved solution that is 0.5 mL. From research-grade powder at 20 mg/mL it is 2 mL. The reduced renal dose of 20 mg is 0.25 mL of the approved solution, or 1 mL at 20 mg/mL [8].
Pro tip
Always add the bacteriostatic water slowly, letting it run down the side of the vial. Never shake the vial -- swirl gently to avoid damaging the peptide.
Location
Site 01
Abdomen
Pinch the skin 2 inches from navel. Avoid the area directly around the belly button. Rotate between left and right sides.
Site 02
Outer Thigh
Middle third of the outer thigh. Keep at least 4 inches above the knee and below the hip. Alternate legs each injection.
Site 03
Upper Arm
Back or outer area of the upper arm. This site may require assistance from another person for proper technique.
Rotate between 3 sites to prevent tissue buildup and ensure consistent absorption.
Pro tip
Rotate your injection sites with each dose to prevent lipohypertrophy (buildup of fatty tissue). Keep a simple log of where you last injected.
Step by step
Wash your hands thoroughly with soap and water
Clean the injection site with an alcohol swab and let it air dry completely
Pinch about an inch of skin to create a fold of fatty tissue
Insert the needle at a 45-90 degree angle (45 if lean, 90 if you have more subcutaneous tissue)
Inject the solution slowly and steadily
Wait 5-10 seconds before withdrawing the needle
Apply light pressure with a clean swab if needed—do not rub
Pro tip
This peptide uses subcutaneous injection (just under the skin)—the standard method used in clinical trials with approximately 92% bioavailability. Inject at a 45-90 degree angle into pinched skin. Aspirate before injecting to ensure you haven't hit a blood vessel.
Timing
Optimal timing
Best time
The label sets no time of day — one injection daily, at a consistent time [8]. The morning preference previously published here had no source behind it; trials dosed once daily without a specified time [13].
With food?
Food is irrelevant to a subcutaneous injection and the label sets no food restriction [8].
Stacking notes
If you are injecting more than one peptide, use separate sites. The SS-31 and NMN pairing often quoted for mitochondrial support was tested in aged mice, not people: SS-31 improved diastolic function, NMN improved systolic function, and the combination produced both effects along with higher NAD(H) levels [19]. No human trial has tested elamipretide alongside another peptide.
Sample daily schedule
Any time — the same time each day
40 mg injection
Site: Abdomen, at least 2 inches from the navel, or the outer thigh — rotate daily
The label specifies one subcutaneous injection a day into the abdomen, at least 2 inches from the navel, or the outer thigh, with the site rotated each day. It sets no time of day, and no trial dosed to a clock [8][13]. Peak blood concentration is reached 0.5 to 1 hour after the injection and about 92% of a subcutaneous dose reaches the circulation [8].
Dosing tiers
Dose
40 mg
Frequency
Once daily
Duration
Continuous — 24 weeks in the phase 3 myopathy trial, up to 168 weeks in the Barth syndrome extension
40 mg once daily is both the starting dose and the maximum. No human trial escalated past it, and it is the approved FORZINITY dose for anyone weighing at least 30 kg [8]. The same flat 40 mg subcutaneous daily dose was used in the 12-patient Barth syndrome trial [6], in MMPOWER-2 (30 patients) [11], in the phase 3 MMPOWER-3 (109 on drug, 109 on placebo) [13] and in ReCLAIM-2 (117 on drug, 59 on placebo) [14]. There is no weight-based subcutaneous dose: the mg/kg figures in circulation are intravenous infusion RATES from MMPOWER-1 [12] and the heart-failure study [7], given in hospital over 2 to 4 hours, and the label states the product is not approved for intravenous use [8]. Halve the dose to 20 mg once daily in adults with an eGFR below 30 mL/min who are not on dialysis; it has not been studied in people on dialysis [8].
Preservation
Before mixing
The approved product, FORZINITY, is a ready-to-use solution — 280 mg in 3.5 mL (80 mg/mL) in single-patient vials, four to a carton. It needs no reconstitution. Store it refrigerated at 2-8°C and do not freeze it [8]. Research-grade SS-31 is sold instead as a lyophilised powder; keep that refrigerated at 2-8°C in its sealed vial away from light.
After mixing
Once a FORZINITY vial has been opened, it can be kept refrigerated at 2-8°C or at room temperature between 20-25°C, and must be discarded 8 days after first opening [8]. Reconstituted research-grade powder is a different product with no label behind it; refrigerate it, never freeze it, and protect it from light.
Shelf life after mixing
28 days
Signs of degradation
Discard the vial immediately if you notice any of these:
Cloudiness or haze — the label describes the solution as clear and colourless to yellow [8]
Visible particles
Any colour beyond the clear-to-yellow range the label describes [8]
Important
When to stop
Any sign of a hypersensitivity reaction — skin or respiratory. The label directs discontinuation for a severe reaction and serious hypersensitivity is its only contraindication [8]
An injection-site reaction that spreads, worsens, or shows signs of infection. These drove discontinuation in 7.3% of treated participants in phase 3 against 1.8% on placebo [13]
Your eGFR falling below 30 mL/min — the label halves the dose rather than stopping, but it needs a prescriber's decision [8]
Your prescriber advises discontinuation
Elamipretide is FDA-approved only to improve muscle strength in Barth syndrome, in patients weighing at least 30 kg, and that approval is an accelerated one pending a confirmatory trial [8][9]. Every other use is investigational. It is a prescription injectable — decisions about starting, stopping or adjusting belong with a prescriber.
Clean technique checklist
Wash hands thoroughly with soap and water before handling supplies
Swab vial tops and injection site with alcohol and let dry
Never touch the needle tip or allow it to contact non-sterile surfaces
Use a new syringe and needle for each injection
Dispose of used sharps in a proper sharps container
Store reconstituted peptides according to the storage instructions above
Published research
Tung C, Varzideh F, Farroni E · 2025
This comprehensive review confirmed SS-31's unique ability to selectively bind cardiolipin in mitochondria, stabilizing cristae structure, reducing oxidative stress, and enhancing ATP production. Clinical trials like PROGRESS-HF, TAZPOWER, and MMPOWER-3 demonstrate significant therapeutic potential across multiple conditions involving mitochondrial dysfunction.
Chavez JD, Tang X, Campbell MD · 2020
Using advanced chemical cross-linking and mass spectrometry, researchers mapped exactly which proteins SS-31 interacts with inside mitochondria. All the interacting proteins are known cardiolipin binders involved in either ATP production or metabolic processes—confirming SS-31's highly targeted mechanism of action.
Mitchell W, Tamucci JD, Ng EL · 2022
This study analyzed how SS-31's specific amino acid sequence affects its activity. The research showed SS-31 modulates membrane electrostatics and can permeate cells to target mitochondria. All tested peptide variants were pharmacologically active in restoring mitochondrial membrane potential and promoting cell survival under stress.
Gu Q, Wang Y, Zhang H · 2025
At 5 mg/kg daily, SS-31 significantly reduced lung fibrosis in mice by protecting mitochondrial structure and function. The peptide reduced oxidative stress markers, inflammatory factors (TNF-alpha, IL-1beta, IL-6), and improved overall lung tissue health—demonstrating its potential beyond cardiac applications.
Ravenscraft B, Lee DH, Dai H · 2025
SS-31 protected neurons from mitochondrial dysfunction and cell death in both laboratory and animal models of spinal cord injury. The peptide reduced cardiolipin loss, prevented neurite degeneration, and improved behavioral recovery—highlighting its neuroprotective potential.
Reid Thompson W, Hornby B, Manuel R, et al. · 2021
Twelve patients with Barth syndrome took 40 mg/day elamipretide and placebo for 12 weeks each in random order, separated by a 4-week washout. Neither primary endpoint was met in that blinded phase. Ten patients continued on 40 mg/day in an open-label extension, and at week 36 there were improvements in 6-minute walk distance (+95.9 m, p=0.024) and on the Barth Syndrome Symptom Assessment (-2.1 points, p=0.031), along with knee extensor strength, patient global impression and some cardiac parameters. The open-label result has no control arm.
Daubert MA, Yow E, Dunn G, et al. · 2017
Thirty-two patients with heart failure and an ejection fraction of 35% or less received a single 4-hour intravenous infusion of elamipretide at 0.005, 0.05 or 0.25 mg/kg/hour (8 per cohort) or placebo (12). This is an infusion RATE used inside a hospital, not a dose anyone measures out. There were no serious adverse events, and blood pressure and heart rate stayed stable in every cohort. Compared with placebo, the highest-rate cohort showed a 18 mL fall in left ventricular end-diastolic volume (p=0.009) and a 14 mL fall in end-systolic volume (p=0.005) at the end of the infusion. Elamipretide was undetectable in plasma 24 hours after the infusion started.
U.S. Food and Drug Administration · 2025
FDA prescribing information for FORZINITY (elamipretide), granted accelerated approval in September 2025 to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. The label lists injection site reactions as the most common adverse reactions and reports absolute bioavailability after subcutaneous injection of approximately 92%. Continued approval may depend on verification of clinical benefit in a confirmatory trial.
Drug Discoveries & Therapeutics · 2025
On 19 September 2025 the FDA granted accelerated approval to elamipretide for Barth syndrome — the first approved therapy directed at the mitochondrial cause of the disease. The paper notes that in the randomised, double-blind, placebo-controlled crossover trial elamipretide produced no significant improvement in the 6-minute walk test or fatigue scores, and that the sustained benefits were seen in the 168-week open-label extension. The most common adverse events were mild injection-site reactions. A confirmatory trial is a condition of the approval.
Hornby B, Reid Thompson W, Almuqbil M, et al. · 2024
Ten patients with Barth syndrome entered the open-label extension of TAZPOWER on 40 mg subcutaneous elamipretide daily and eight reached the week-168 visit. Injection-site reactions were the most common adverse event. Six-minute walk distance improved at every extension timepoint, cumulatively 96.1 m by week 168 (p=0.003), fatigue scores stayed below baseline throughout, and three-dimensional left ventricular stroke, end-diastolic and end-systolic volumes improved from baseline to week 168.
Karaa A, Haas R, Goldstein A, et al. · 2020
Thirty adults with genetically confirmed primary mitochondrial myopathy took 40 mg/day subcutaneous elamipretide for 4 weeks and placebo for 4 weeks in random order, separated by a 4-week washout. The primary endpoint was missed: 398.3 m walked on elamipretide against 378.5 m on placebo, a 19.8 m difference (95% CI -2.8 to 42.5, p=0.0833). Patient-reported fatigue and muscle complaints did improve against placebo (p=0.0006 and p=0.0018). Injection-site reactions were the most common adverse event at 80%, mostly mild; there were no serious adverse events and no deaths.
Karaa A, Haas R, Goldstein A, et al. · 2018
Thirty-six adults with genetically confirmed primary mitochondrial myopathy received intravenous elamipretide at 0.01, 0.1 or 0.25 mg/kg/hour, or placebo, over 2 hours in a dose-escalating sequence for 5 days. Again these are infusion rates, not self-administered doses. The highest rate produced a mean 64.5 m improvement in 6-minute walk distance at day 5 against 20.4 m on placebo (p=0.053), with a dose-dependent trend across rates (p=0.014). No other efficacy or safety endpoint differed. This study set the exposure that the later 40 mg/day subcutaneous trials were built on.
Karaa A, Bertini E, Carelli V · 2023
In this 24-week phase 3 trial, 218 adults with primary mitochondrial myopathy received 40 mg/day subcutaneous elamipretide or placebo. Elamipretide did not improve six-minute walk distance or total fatigue score compared with placebo. Most adverse events were mild or moderate, and injection site reactions were the only adverse events reported in more than 10% of treated participants.
Allingham MJ, Mettu PS, Cousins SW, et al. · 2024
One hundred and seventy-six patients aged 55 or over with dry age-related macular degeneration and non-central geographic atrophy took 40 mg subcutaneous elamipretide daily (117) or placebo (59) for 48 weeks. Neither primary endpoint was met. Adverse events were reported in 86% of the elamipretide group and 71% of the placebo group, the most common being injection-site reactions — itching, pain, bruising and redness. Pre-specified analyses showed less progression of ellipsoid zone loss on elamipretide, which is the endpoint the phase 3 programme adopted.
Mitchell W, Ng EA, Tamucci JD · 2020
This biophysical study reports that SS-31 accumulates 1,000- to 5,000-fold at the inner mitochondrial membrane. Its binding to anionic lipids such as cardiolipin changes membrane surface electrostatics, which the authors identify as a key component of how the peptide works.
Ahmadpour ST, Maheo K, Servais S · 2020
This review states that cardiolipin is a mitochondria-specific phospholipid comprising about 20% of the inner mitochondrial membrane, and describes its role in organizing respiratory chain complexes and mitochondrial membrane structure.
Yoo Y, Yeon M, Yoon MS · 2025
This review reports that cardiolipin accounts for roughly 18% of inner mitochondrial membrane mass, that cardiolipin levels are reduced in aged skeletal muscle alongside impaired respiratory capacity and structural degradation, and that cardiolipin depletion disrupts cristae organization, lowers electron transport chain efficiency and increases reactive oxygen species production.
Li Y, Berliocchi L, Li Z · 2023
This review treats mitochondrial dysfunction as one of the established hallmarks of aging and examines how it interacts with the other hallmarks, describing it as one of the most important drivers of cellular aging.
Whitson JA, Bitto A, Zhang H · 2020
In aged mice, SS-31 improved diastolic heart function while nicotinamide mononucleotide (NMN) improved systolic function at high workload. The combination produced both effects and raised steady-state NAD(H) levels more than either drug alone, leading the authors to conclude that combined treatment may be more effective for age-related cardiac dysfunction than either agent given alone.
Smuder AJ, Roberts BM, Wiggs MP · 2020
In mice bearing colon-26 tumors, daily SS-31 preserved body weight and muscle weights, prevented atrophy of type I and type IIa muscle fibers, and prevented the loss of diaphragm and limb muscle function seen in untreated tumor-bearing mice, alongside reduced mitochondrial reactive oxygen species production.
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