SS-31, the peptide that goes to the mitochondria: what it is and how its trials came out
· Novatheris
SS-31 comes up a lot in conversations about energy and aging. It is almost always told halfway: people talk about what it did in mice and skip what happened in the trials with people. This article puts both parts together, with their sources, and marks where what is known ends.
It has something that sets it apart from almost every research peptide: it was actually tested in large, randomized, placebo-controlled trials. That makes it possible to see clearly what was measured, and also what did not work out.
What SS-31 is
SS-31 is a peptide of only four pieces, what is called a tetrapeptide. In the literature it also appears as elamipretide, MTP-131 or Bendavia (Tung et al., 2025).
Most peptides work like a key that fits a lock on the surface of the cell. SS-31 does not. It gets inside the cell and concentrates in the inner membrane of the mitochondria, the part of the cell that produces energy (Tung et al., 2025).
Cardiolipin, its target
In that inner membrane, SS-31 binds cardiolipin. It is a fat that helps hold up the folds of the membrane and the machinery that makes ATP, the molecule the cell uses as its energy currency (Tung et al., 2025).
The idea being researched is simple to state: if cardiolipin is damaged, the mitochondria work worse. A peptide that sticks to it might help keep that machinery in place. That is the hypothesis. What follows is what was measured.
What was seen in mice
The two most cited papers are in old mice.
- In 27-month-old mice, which is old age for a mouse, a single dose of SS-31 quickly improved the energy output of muscle mitochondria and muscle performance (Siegel et al., 2013).
- In old female mice treated for 8 weeks, SS-31 lowered age-related oxidative stress and improved exercise tolerance (Campbell et al., 2019).
These are animal results, with a route of administration that is not the one used in people. An old mouse is not an old person, and what happens in a cage does not carry over on its own.
The closest thing to healthy people
The study that comes closest to people without a disease is this one. It included 39 older adults, 60 to 85 years old, chosen because their mitochondria performed poorly, not because they were sick (Roshanravan et al., 2021).
They received a single intravenous administration. This is what was measured:
- ATP production in muscle improved.
- By day 7 that effect was gone.
- The muscle's resistance to fatigue did not improve, even though ATP had gone up.
It is a single-dose study. It says nothing about repeated administration, about young people, or about athletic performance.
The large trials: almost none met their goals
This is the part that gets left out the most. SS-31 was also tested in other diseases, such as heart failure in the PROGRESS-HF trial (Tung et al., 2025). Here are three controlled trials with published results, and in all three the primary goal was not met.
Mitochondrial myopathy. A genetic disease in which muscle mitochondria fail. The MMPOWER-3 trial, with 218 patients over 24 weeks, measured the 6-minute walk distance and fatigue. Neither improved versus placebo: the difference in the walk was -3.2 meters (Karaa et al., 2023).
Dry macular degeneration. An eye disease that gradually damages the retina. The ReCLAIM-2 trial, with 176 patients over 48 weeks, missed both primary endpoints: visual acuity and growth of the damaged area. What did move was a secondary measure, the preservation of a retinal layer called the ellipsoid zone (Ehlers et al., 2024). A secondary result is useful for asking a new question, not for treating the first one as answered.
Barth syndrome. A rare genetic disease in which cardiolipin is made incorrectly. That made it the most logical case for this peptide. The placebo part of the TAZPOWER trial, with 12 patients in a crossover design, missed its primary endpoints (Reid Thompson et al., 2021).
The improvements reported in Barth come from another part of the same work: an open-label extension, where everyone received the peptide and everyone knew it. There, the 6-minute walk rose by 95.9 meters at 36 weeks (Reid Thompson et al., 2021). Then came a comparison with untreated Barth patients taken from historical records (Hornby et al., 2022). Neither has a placebo, and without a placebo it is hard to separate the effect of the peptide from the effect of knowing you are being treated.
Why it matters to read it this way
With many peptides the problem is that there are no trials. With SS-31 there are trials, and what they say is more modest than what gets repeated.
That does not make it useless for research. It makes it a compound with clear questions: why an effect seen in mice and in measured ATP did not turn into better results in the placebo-controlled trials. To see it side by side with another mitochondrial peptide, the article on MOTS-c and SS-31 puts the two together.
What is still unknown
For the notebook:
- The study in older adults says the effect was gone by day 7, as expected from the half-life of SS-31 in human blood, but its abstract does not give that number (Roshanravan et al., 2021).
- We found no studies in young, healthy people.
- The repeated-administration trials we reviewed were in people with a disease: mitochondrial myopathy, Barth syndrome, dry macular degeneration and heart failure (Tung et al., 2025).
- In the three controlled trials in this article, the primary goal was not met.
- The study in older adults without disease used a single administration, and the effect disappeared within a week (Roshanravan et al., 2021).
How it is stored
SS-31 comes lyophilized, which means dry: a powder whose water was removed with cold and vacuum. It is kept at -20 °C, closed and away from bright light. Let the vial reach room temperature before opening it, so no moisture gets in. Once reconstituted, it goes to 2 to 8 °C and for a short time.
SS-31 in Costa Rica: where to find it
The SS-31 page has its chemical data, the storage note and the purity information, with the +99.5% standard we ask of outside laboratories such as Janoshik and Freedom Diagnostics. SS-31 also comes in the Energy kit, together with MOTS-c and NAD+; NAD+ has its own article, what it is and what the studies measured. Delivery takes 2 hours in the GAM and 24 hours in the rest of Costa Rica. For research use only.