Peptide profile · Mitochondrial
SS-31 (Elamipretide)
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 ; phase 3 trials in primary mitochondrial myopathy and in dry age-related macular degeneration missed their primary endpoints .
Molecular formula
C32H49N9O5
- CAS number
- 736992-21-5
- PubChem
- 11764719
- Developed · 2004
- Dr. Hazel Szeto and Dr. Peter Schiller, Weill Cornell Medical College / University of Montreal
Amino acid sequence
D-Arg-dimethylTyr-Lys-Phe-NH240mg
Every documented dose level
| Phase | Dose | Frequency |
|---|---|---|
| Continuous — 24 weeks in the phase 3 myopathy trial, up to 168 weeks in the Barth syndrome extension | 40 mg | Once daily |
Best for mitochondrial health optimization & cellular energy enhancement
Best for
Mitochondrial Health Enthusiasts
If you're focused on optimizing cellular energy at the most fundamental level, SS-31 targets the actual machinery inside your mitochondria. It binds to cardiolipin—the special fat molecule that holds your electron transport chain together—keeping your cellular powerhouses running smoothly .
Aging Adults Concerned About Cellular Decline
Mitochondrial dysfunction is now recognized as a hallmark of aging . Your cells' energy factories get less efficient over time, producing more harmful byproducts. SS-31 helps protect and restore mitochondrial function, addressing one of the root causes of age-related decline .
Heart Health Supporters
Your heart is one of the most energy-demanding organs, packed with mitochondria. Clinical trials have studied SS-31 in heart failure patients because cardiac cells are especially vulnerable to mitochondrial dysfunction . Supporting heart mitochondria supports overall cardiovascular function.
Those Recovering from Oxidative Stress
Whether from intense exercise, illness, or environmental factors, oxidative stress damages your mitochondria from the inside out. SS-31 works as an antioxidant exactly where reactive oxygen species are produced—right at the inner mitochondrial membrane—neutralizing them before they cause harm .
Consider alternatives if
Do not use if
- You have had a serious hypersensitivity reaction to elamipretide or any excipient — the label's only contraindication
- The patient is a neonate — the formulation contains benzyl alcohol
- You are pregnant or breastfeeding — there is no human data; the label's animal studies showed no developmental effects at 4 to 10 times the clinical exposure
- Body weight is under 30 kg — outside the approved indication and untested
Use with caution if
- Your eGFR is below 30 mL/min and you are not on dialysis — the label halves the dose to 20 mg once daily
- You are on dialysis — elamipretide has not been studied in renal failure on dialysis
- You are 65 or over — no elamipretide trial enrolled that age group
- You are taking anything else — the label reports interaction studies only for aspirin, clopidogrel and heparin, all negative, and carries no drug-interactions section
Not sure?
Compare SS-31 (Elamipretide) with similar peptides to find the best fit for your goals.
Route
Subcutaneous injection (just under the skin)—the standard method used in clinical trials with approximately 92% bioavailability
Best sites
- Abdominal area (about 2 inches away from the belly button)
- Front or outer thigh (middle section)
- Back of the upper arm
The SS-31 (Elamipretide) injection guide covers reconstitution · step-by-step technique · storage · a sample daily schedule.
1 common side effect · 1 serious
In the 24-week phase 3 trial in primary mitochondrial myopathy, adverse events were reported by 98.2% (107 of 109) of participants on elamipretide against 76.1% (83 of 109) on placebo, and injection-site reactions were the only adverse event above 10% in the treated group.
Serious adverse events were 4.6% (5 of 109) against 2.8% (3 of 109) and none were judged treatment-related; discontinuation for an adverse event was 7.3% (8 of 109) against 1.8% (2 of 109). There were no deaths and no hospitalisations .
In the 12-patient Barth syndrome crossover trial behind the approval, every patient had an injection-site reaction on elamipretide — 12 of 12 (100%) against 8 of 12 (67%) on placebo — with erythema 100% against 25% and induration 67% against 17% .
The label carries two warnings: serious hypersensitivity reactions, and benzyl alcohol toxicity, for which the product is not approved in neonates. It also reports blood eosinophil counts rising during treatment, peaking around day 90 and returning to normal over 6 to 12 months .
Every safety figure above comes from company-run trials in diagnosed patients: 218 adults with primary mitochondrial myopathy over 24 weeks , 176 adults with dry age-related macular degeneration over 48 weeks , and 12 patients with Barth syndrome followed into a 168-week open-label extension .
No elamipretide trial enrolled anyone aged 65 or over, none enrolled healthy people, and there is no human pregnancy data — the label's reassurance there is from animal studies at 4 to 10 times the clinical exposure .
Nothing has been published on elamipretide for ageing, athletic performance or general mitochondrial support, so the safety record above does not extend to those uses.
Common side effects · experienced by some users
Injection site reactions
The only adverse event reported by more than 10% of treated participants in the phase 3 myopathy trial , and universal in the Barth syndrome trial — 12 of 12 (100%) on elamipretide against 8 of 12 (67%) on placebo, with erythema 100% against 25%, pain 75% against 42%, induration and itching 67% against 17%, and bruising and hives 25% against none . Swelling, bleeding and injection-site nodules were also recorded .
Management
Rotate daily between the four quadrants of the abdomen and the outer thighs, as the label directs and as trial participants were instructed to do . Injection-site reactions were the main reason for discontinuation in the phase 3 trial, at 7.3% against 1.8% on placebo .
Serious side effects
Hypersensitivity reaction
The label warns that serious allergic reactions requiring emergency medical intervention have been reported, with skin and respiratory manifestations. Serious hypersensitivity to elamipretide or any excipient is the label's only contraindication .
Management
Stop immediately and seek emergency care. The label directs discontinuation if a severe reaction occurs .
These typically resolve with continued use or dose adjustment.
Stop and seek help if
- Any sign of a hypersensitivity reaction — skin or respiratory. The label directs discontinuation for a severe reaction and serious hypersensitivity is its only contraindication
- 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
- Your eGFR falling below 30 mL/min — the label halves the dose rather than stopping, but it needs a prescriber's decision
- 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 . Every other use is investigational. It is a prescription injectable — decisions about starting, stopping or adjusting belong with a prescriber.
With other peptides
With medications
- SafeAspirin, clopidogrel, heparin — The only drug-interaction studies on the FDA label. None showed a significant interaction with elamipretide .
- CautionEverything else — The label carries no drug-interactions section beyond those three. Elamipretide and its two inactive metabolites are cleared renally — about 100% of a dose is recovered in urine by 48 hours — and the label halves the dose below an eGFR of 30 mL/min, so anything that loads the kidneys is worth raising with a prescriber .
Strong human trials · first signs weeks 1-4
Evidence level
Strong human trials
(Phase 3 or FDA approved)
100/100
Regulatory status
FDA approved as FORZINITY for Barth syndrome (accelerated approval, 19 September 2025); every other use is investigational
Onset of effects
Not established outside Barth syndrome
How it works
Think of your cells like tiny cities, and mitochondria are the power plants that keep everything running.
Inside each power plant is a special membrane with folds called cristae—this is where your cells actually make energy (ATP). A fatty molecule called cardiolipin holds this whole structure together like molecular glue.
As we age or face stress, cardiolipin gets damaged and the power plant structure falls apart, making less energy and more pollution (oxidative stress) . SS-31 is like a repair crew that goes directly to the cardiolipin and stabilizes it .
When the structure stays intact, your power plants work better—more energy, less cellular pollution, healthier cells .
The deeper mechanism
Elamipretide (SS-31) is a synthetic tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) with unique cell-penetrating and mitochondria-targeting properties .
Its alternating cationic (Arg, Lys) and aromatic (dimethylTyr, Phe) residues enable rapid cellular uptake independent of mitochondrial membrane potential and selective accumulation (several thousand-fold) in the inner mitochondrial membrane (IMM) .
SS-31 selectively binds to cardiolipin (CL), an anionic phospholipid unique to the IMM that constitutes approximately 20% of IMM lipid content .
CL is essential for: (1) organizing respiratory chain supercomplexes, (2) maintaining cristae ultrastructure, and (3) proper function of cytochrome c oxidase and other electron transport chain components .
By stabilizing CL and modifying membrane electrostatics, SS-31 optimizes electron transfer efficiency, increases ATP synthesis, and reduces electron leak that generates reactive oxygen species (ROS) .
Additionally, SS-31 prevents CL peroxidation and translocation to the outer membrane—processes that would otherwise trigger cytochrome c release and apoptosis .
Cross-linking mass spectrometry has identified SS-31 binding partners including ATP synthase, complex III, complex IV, and enzymes in 2-oxoglutarate metabolism, all of which are established CL-interacting proteins .
This multi-target mechanism explains SS-31's broad therapeutic potential across conditions involving mitochondrial dysfunction .
What to expect
Weeks 1-4
What you might notice
What's normal
Weeks 12-24
What you might notice
- This is where the controlled trials ended, and where they found nothing: both primary endpoints missed at 12 weeks in Barth syndrome and at 24 weeks in the 218-patient phase 3 trial
- Patient-reported fatigue improved against placebo in the smaller phase 2 crossover, though the walking endpoint did not
What's normal
Week 36 onward
What you might notice
- The reported gains in Barth syndrome all come from this window and all come without a control arm: +95.9 m on the six-minute walk test at week 36 , cumulatively +96.1 m by week 168
- Knee extensor strength rose by a median 34 to 68 newtons during the extension — the measure the FDA granted accelerated approval on
Signs it's working
What the trials measured
Signs it's working
What has never been measured
Not seeing results?
Common reasons
- The controlled trials did not find an effect. Both primary endpoints were missed in the 12-week Barth syndrome crossover and in the 24-week phase 3 trial in 218 adults — a compound working as advertised is not the baseline assumption here
- Elamipretide has only been shown to do anything in diagnosed mitochondrial disease. There is no published trial in healthy people, in ageing, or in athletic performance
- Inconsistent daily dosing — the label and every trial dose once a day, every day
- The dose does not go up. 40 mg once daily is the ceiling in every human trial and on the label; there is no next step to try
- Research-grade material with no certificate of analysis. The approved product is a prescription 80 mg/mL solution; anything else is unverified
33 registered studies, 2 still enrolling.
By phase
A trial spanning two phases is counted in both, so these can sum above the total. Observational studies carry no phase.
What kind of research
About 2,231 people took part in the studies that actually administered SS-31 (Elamipretide). Observational studies analyse the records of people already taking it — nobody was given anything for the study, so they are counted separately and cannot show cause and effect.
Most recent
Clinical Trial in Patients With Barth Syndrome- 4TAZPower
Stealth BioTherapeutics Inc.
- ISRCTN84705575 48 enrolled
A Phase IIIb/IV, randomized, double-blind, parallel-group, placebo-controlled, trial to evaluate the efficacy and safety of daily subcutaneous injections of elamipretide in patients with genetically confirmed Barth syndrome
Stealth BioTherapeutics (United States)
Study of Healthy Aging and Physical Function With Elamipretide
David Marcinek
Sources: ClinicalTrials.gov, the EU Clinical Trials Information System and ISRCTN, deduplicated so a study registered twice is counted once. A study is counted when SS-31 (Elamipretide) is named as an intervention; studies that only mention it in passing are not.
What makes SS-31 different from other mitochondrial supplements like CoQ10?
CoQ10 is an electron carrier that participates in the electron transport chain, while SS-31 targets the structural foundation—cardiolipin—that holds the entire energy-producing machinery together . Think of CoQ10 as providing fuel, while SS-31 repairs and maintains the engine itself. They work through completely different mechanisms and can actually complement each other.
Is SS-31 FDA approved?
Yes, elamipretide (the pharmaceutical name for SS-31) received FDA approval in September 2025 for treating Barth syndrome, a rare genetic mitochondrial disorder . This makes it the first FDA-approved medication specifically targeting mitochondria . For other uses like general anti-aging or performance, it remains a research compound.
How long does it take to feel effects from SS-31?
No trial has measured how quickly a healthy person feels anything, because no trial has enrolled healthy people. In patients, the blinded phases came back empty: the 4-week crossover in mitochondrial myopathy missed its walking endpoint , the 12-week Barth syndrome crossover missed both of its primary endpoints , and the 24-week phase 3 trial missed both of its own . The gains that were reported came later and without a control arm — 6-minute walk distance improved cumulatively by 96.1 m over 168 weeks of open-label treatment in Barth syndrome . Anyone promising an effect in two to four weeks is not quoting a trial.
Can I take SS-31 if I don't have a mitochondrial disease?
SS-31's FDA approval is specifically for Barth syndrome, but research interest extends to general mitochondrial dysfunction associated with aging, heart failure, and other conditions . For healthy individuals interested in mitochondrial optimization, it remains a research compound and should only be used under medical supervision.
Why is SS-31 injected rather than taken orally?
As a peptide, SS-31 would be broken down by digestive enzymes if taken orally. Subcutaneous injection allows the full molecule to enter your bloodstream intact, achieving approximately 92% bioavailability . The peptide then crosses cell membranes and concentrates specifically in mitochondria .
Does SS-31 have any effects on weight or body composition?
SS-31 isn't a weight loss compound, but by improving mitochondrial function it could theoretically support better metabolism. Some research in cancer cachexia (muscle wasting) showed SS-31 helped preserve muscle mass by maintaining mitochondrial energy production . However, it's not marketed or studied primarily for weight management.
Can SS-31 help with brain health and cognitive function?
Research shows SS-31 has neuroprotective effects in models of spinal cord injury and neurodegeneration . Your brain cells are packed with mitochondria and highly sensitive to energy deficits. By protecting brain mitochondria, SS-31 could theoretically support cognitive health, though more human studies are needed.
Is it safe to use SS-31 long-term?
The longest published follow-up is 168 weeks: ten Barth syndrome patients entered an open-label extension on 40 mg daily and eight reached week 168, with injection-site reactions the most common adverse event throughout . The 24-week phase 3 trial in 218 adults found serious adverse events in 4.6% on elamipretide against 2.8% on placebo, none treatment-related, and no deaths or hospitalisations . That record is from diagnosed patients under trial supervision. There is no long-term data in healthy people, and none in anyone over 65 — no elamipretide trial enrolled that age group .
Ready for the protocol?
Every dosing tier, administration route, timing note, and dose-adjustment rule for SS-31 (Elamipretide), on one page.
SS-31 (Elamipretide) dosing protocol