SS-31

What SS-31 is

SS-31 is a small synthetic peptide, four amino acids long (D-Arg-dimethylTyr-Lys-Phe-NH2). It shows up under several names: elamipretide, MTP-131, Bendavia in older papers and, since September 2025, the brand name Forzinity. It belongs to the Szeto-Schiller (SS) family of peptides, named for the researchers who developed them. Their alternating pattern of positively charged and aromatic amino acids lets them reach the inner membrane of mitochondria.

Two deeper pages cover how SS-31 binds cardiolipin and the research on SS-31 and ATP production. For how it compares with MOTS-c, see our overview of mitochondrial peptides.

How it works

Cardiolipin is a phospholipid found only on the inner mitochondrial membrane. It helps fold that membrane into cristae and holds the respiratory complexes together so they can make ATP efficiently. When cardiolipin is damaged, cytochrome c (an electron carrier in the chain) can bind it in a way that turns cytochrome c into a peroxidase, which in turn damages more cardiolipin.

A 2014 review by Hazel Szeto in the British Journal of Pharmacology describes SS-31 binding cardiolipin through electrostatic and hydrophobic interactions. In cell and animal studies, that binding kept cytochrome c working as an electron carrier. It also protected the cristae and improved oxidative phosphorylation. Much of the animal work is in ischemia-reperfusion injury, such as smaller heart-attack damage in rabbits and sheep.

FDA describes the approved drug the same way: it works "by binding to the inner part of the mitochondria, improving mitochondrial structure and function." The mechanism is well characterized in cells and animals; showing a clear benefit in people has been harder.

Human trials

The trials behind SS-31's current status enrolled people with rare mitochondrial diseases or eye disease. All used 40-60 mg given by subcutaneous injection once a day. We found no published trial in healthy adults or athletes.

Barth syndrome and the approval

Barth syndrome is a rare inherited mitochondrial disease that mostly affects males. Stealth BioTherapeutics, the developer, estimates one case per million male births. According to FDA's Drug Trials Snapshot, the approval rests on one trial, SPIBA-201, in 12 males aged 12 and older at a single US site.

• In the 28-week, placebo-controlled crossover part, 40 mg a day was not better than placebo on either primary endpoint: six-minute walk distance and a fatigue score.
• Knee-extensor strength, a secondary endpoint, barely moved during the controlled part (median +4 newtons on drug vs. -5 on placebo at week 12). It rose in the open-label extension, which had no placebo group, with median increases of 34 to 68 newtons from a baseline of 124 in the 8-10 patients who continued.

FDA granted accelerated approval to Forzinity on September 19, 2025, for patients with Barth syndrome who weigh at least 30 kg. Accelerated approval means FDA judged the knee-strength change "reasonably likely" to predict real benefit, such as walking farther. It also required a randomized, placebo-controlled trial to confirm that benefit. Stealth calls Forzinity the first FDA-approved mitochondria-targeted therapy.

In its April 2026 update, Stealth reported that 33 US patients had started the drug. The first site of the confirmatory Phase 4 trial had opened in the UK, and a dosing study in children under 30 kg was planned for 2026.

Primary mitochondrial myopathy

MMPOWER-3 was a 24-week Phase 3 trial of 40 mg daily in adults with primary mitochondrial myopathy, a genetically mixed group. It missed its primary endpoints (six-minute walk and fatigue). A post hoc analysis published in 2024 looked at people whose mutations affect the genes that copy mitochondrial DNA (mostly POLG and TWNK). They walked about 25 meters farther on elamipretide, compared with about 2 meters on placebo (p = 0.06, just short of significance). Post hoc subgroup results generate hypotheses; they don't prove an effect.

That analysis led to NuPOWER, a 48-week Phase 3 trial of 60 mg daily in 102 adults with mitochondrial disease caused by nuclear DNA mutations, completed in December 2024. Stealth presented the results at the Euromit meeting in June 2026 as supporting further work in the POLG1 subgroup. As of October 2026, the company is drafting a new, narrower trial for POLG-related myopathy at FDA's request, one meant to support approval.

Dry age-related macular degeneration

ReCLAIM-2 was a Phase 2 trial in 176 people aged 55 and older with geographic atrophy, given 40 mg daily for 48 weeks. It missed both primary endpoints: low-light visual acuity and growth of the atrophic area. On a predefined additional measure, elamipretide slowed loss of the ellipsoid zone, a retinal layer that reflects photoreceptor health, by 43% compared with placebo. The authors say that measure will be the primary endpoint of the Phase 3 program. As of October 2026, the Phase 3 ReNEW trial is fully enrolled, and Stealth expects results in late 2027.

Side effects in trials

Injection-site reactions dominate. In the controlled part of the Barth trial, all 12 patients had injection-site redness on SS-31, compared with 3 of 12 on placebo. Pain was reported by 9 vs. 5. Hardening and itching each affected 8 vs. 2. In ReCLAIM-2, 86% of the elamipretide group reported an adverse event vs. 71% on placebo, mostly injection-site reactions.

The prescribing information, as summarized by Stealth, warns about allergic reactions, some needing emergency care, that can start minutes to months into treatment. It also notes modest rises in eosinophils (a type of white blood cell) peaking around 90 days, without symptoms. The approved product contains benzyl alcohol and isn't approved for newborns.

What users report

Outside trials, SS-31 is sold as a research-use-only powder, and community use looks very different. In a GLP-1 Forum thread from late 2024, users describe starting around 0.5-2 mg a day and working up to about 4 mg a day for roughly four weeks. Several then switched to MOTS-c (see our MOTS-c research notes). One poster described a protocol that moved to 10 mg a day for 20 days. Several said they started SS-31 to counter fatigue while taking tirzepatide.

Reported effects vary. Some posters describe feeling more awake within minutes of a morning dose. Others say raising the dose too fast caused brain fog, and one described daily headaches and exhaustion at 1-2 mg a day. These are self-reports from a self-selected group, with no placebo comparison and products of unknown purity.

The gap between users and research is large. Community doses are roughly a tenth of the 40 mg trial dose, and the people using them are mostly healthy adults, a group no trial we found has studied. No trial measured energy within minutes of a dose, and expectation effects are a plausible explanation for some of what users describe. Research-use-only vials also aren't made under the approved drug's manufacturing controls.

Legal and sport status

As of October 2026, elamipretide is an FDA-approved prescription drug in the US only for Barth syndrome in patients weighing at least 30 kg. Every other use is investigational. We found no EU approval; Stealth notes that no Barth syndrome treatment is approved by the European Medicines Agency.

The approval hasn't made gray-market sales safer for sellers. In an August 24, 2026 warning letter to one online peptide seller, FDA listed "SS-31 (Elamipretide)" among unapproved new drugs. The letter said the seller's "research use only" labels didn't change that, citing claims on its website about what the compound does in the body and its sale of bacteriostatic water for reconstitution.

For tested athletes, the picture is unclear. As of October 2026, our understanding is that WADA's Prohibited List doesn't name elamipretide. Before approval it fell under S0, the catch-all for substances with no government approval for human therapeutic use. Now that it's approved in the US, it's not clear whether S0 still applies, and we couldn't confirm WADA's or USADA's position.

What we still don't know

• Whether the knee-strength change in Barth syndrome translates into better walking or daily function. The confirmatory trial is designed to answer this.
• Whether a narrower trial in POLG-related myopathy succeeds after MMPOWER-3 missed its primary endpoints.
• Whether ReNEW confirms the ellipsoid-zone signal in dry macular degeneration when it reads out, expected in late 2027.
• Whether any of this applies to healthy people at 1-5 mg a day. We found no study that tested it, and much of the mechanism work was done in damaged or diseased tissue.