SS-31 Side Effects: What the Trials Found

SS-31 side effects are mostly reactions where the shot goes in: redness, itching, pain, swelling, or a firm spot. In trials of manufactured elamipretide—the clinical name for SS-31—these reactions were common and usually mild to moderate. That isn't the same as risk-free. The Forzinity label also warns about allergic reactions that can be serious, and the evidence comes from small, specific patient groups. Compounded SS-31 has no clinical safety data of its own, so its risks cannot be read straight across from the brand's label.

This page stays with safety. The separate guide to SS-31 benefits covers what the trials did and did not show about outcomes.

SS-31 side effects in the Forzinity label

First, it helps to keep the products straight. In September 2025, the FDA granted accelerated approval—a pathway that requires another study to confirm benefit—to Forzinity for improving muscle strength in people with Barth syndrome, a rare inherited mitochondrial disease, who weigh at least 30 kilograms. Promise's SS-31 is dispensed as a compounded medication, which is different from an FDA-approved product: the formulation offered here is not FDA-approved. A formulation is the exact mixture in the vial.

The Forzinity prescribing information describes a safety group of just 12 males, ages 12 to 35. In the crossover study—meaning each person received elamipretide and an inactive placebo during different periods—all 12 had at least one local reaction while receiving elamipretide. Eight also had a local reaction during placebo treatment, so not every sore or red spot came from the active drug alone.

Those percentages look precise, but each person represents more than eight percentage points. They describe one manufactured product, one dose, and one rare disease—not every use of SS-31.

When a skin reaction may be more than irritation

The label separates ordinary local reactions from hypersensitivity, which means an immune-driven allergic reaction. Reported allergic reactions included rash, raised bumps, eczema-like irritated skin, and cough. Some required emergency treatment, and the label says they appeared anywhere from minutes to months after treatment began. A reaction that spreads beyond the injection site or comes with breathing symptoms deserves a different level of attention than a small sore patch.

Blood tests sometimes showed more eosinophils, a type of white blood cell involved in allergic responses. In studies lasting at least 30 days, counts generally peaked near day 90 and returned to baseline after 6 to 12 months of continued treatment or after treatment stopped. The label says the rise was not linked to symptoms or other laboratory changes.

Forzinity also contains benzyl alcohol as a preservative, and its label warns about benzyl-alcohol toxicity in premature and low-birth-weight newborns exposed to medicines containing it through a vein. Forzinity is not for newborns or intravenous use. This warning belongs to that branded formulation; it does not establish what a compounded SS-31 formulation contains.

What the larger failed programs add

The larger trials make the injection-site pattern harder to dismiss as a quirk of 12 people. They also show why “well tolerated” needs numbers beside it. In a trial report, an adverse event is any medical problem recorded during the study, whether or not the drug caused it.

In the 2020 MMPOWER-2 crossover trial of 30 adults with primary mitochondrial myopathy, a disease that weakens muscles by disrupting cell energy production, 8 in 10 had an injection-site reaction. Redness affected 57%, itching 47%, and pain 20%. Most reactions were mild, but one person stopped because of moderate injection-site pain; there were no serious adverse events or deaths (Karaa et al., Journal of Cachexia, Sarcopenia and Muscle 2020).

MMPOWER-3 followed 218 adults for 24 weeks, with 109 receiving elamipretide and 109 receiving placebo. Redness at the injection site occurred in 86.2% versus 28.4%, and itching in 75.2% versus 9.2%. Serious adverse events occurred in 4.6% versus 2.8%, but none was judged related to treatment. Eight people on elamipretide, or 7.3%, discontinued because of an adverse event versus two on placebo; the treatment-related withdrawals were injection-site events (Karaa et al., Neurology 2023).

The 71-person PROGRESS-HF heart-failure trial lasted 28 days and found similar rates of drug-related adverse events across placebo, 4 mg, and 40 mg groups (Butler et al., Journal of Cardiac Failure 2020). Neither that trial nor MMPOWER-3 met its main treatment goals. That matters because a tolerable drug is not automatically a useful one.

MOTS-c often appears beside SS-31 in mitochondrial discussions, but it is a different peptide with a much thinner human record. Its safety evidence cannot fill gaps in the elamipretide data, just as elamipretide's trial record cannot be borrowed for MOTS-c.

What is still unknown about compounded SS-31

The cleanest answer is also the least comfortable: no clinical trial has tested Promise's compounded SS-31 formulation. Forzinity's reaction rates, preservative warning, dose, and quality controls belong to Forzinity. A compounded preparation is made by a pharmacy for an individual prescription and has its own concentration and ingredients. Brand data can help a prescriber anticipate what the molecule may do, but they cannot prove two formulations have the same safety profile.

The populations studied leave other gaps. The Forzinity program had no pregnant participants, no Barth-syndrome participants 65 or older, and no people with kidney failure on dialysis. Even its long follow-up was tiny: 10 people entered the open-label extension, where everyone knew they were receiving the drug, and eight reached week 168.

As of September 9, 2026, the day this article was written, a July 24, 2026 peer-reviewed SS-31 paper studied irradiated rat heart cells and human heart cells grown from stem cells in laboratory dishes—not people (Xie et al., Journal of Radiation Research 2026). It adds no new clinical side-effect data. Fresh cell findings are interesting, but they do not make the safety gaps smaller.

How to report a reaction so it counts

A small local reaction still belongs in the clinical record, especially if it keeps returning, grows, or makes another injection difficult. The useful details are the vial label, lot number, timing, injection location, what the skin looked or felt like, and how long the reaction lasted.

Trouble breathing, fainting, or a fast-spreading rash are emergency signs; care comes before paperwork. For a non-emergency reaction, the practical route is the prescriber first, then the dispensing pharmacy, followed by an FDA MedWatch report. The step-by-step guide to reporting peptide side effects explains where each report goes.

The decision belongs in the clinical visit

FDA status is one part of the safety picture, not a substitute for judgment. A licensed provider may still prescribe a compounded formulation; that decision is between the patient and the doctor. At Promise, a licensed provider reviews every SS-31 request and not everyone qualifies.

Questions about amounts and trial schedules belong in the SS-31 dosage guide; a side-effect list is not a dosing plan.