SS-31 and ATP Production
What SS-31 does to mitochondrial ATP production in cell, animal and human studies, and why its 2025 approval rested on muscle strength rather than ATP.
How SS-31 relates to ATP output
Mitochondria make most of a cell's ATP by passing electrons along the inner membrane (complexes I to IV) and using the resulting proton gradient to drive ATP synthase. Cardiolipin, an inner-membrane lipid, helps hold these complexes together. SS-31 (elamipretide) binds cardiolipin; how that binding works has its own page. This page covers ATP output.
Damaged cardiolipin lets more electrons leak out and form reactive oxygen species (ROS). By protecting it, SS-31 is thought to improve coupling (ATP made per unit of oxygen) and cut ROS. In these studies, the effect shows up in stressed or aged mitochondria, not healthy young ones.
Findings by tissue and model
| Tissue | Model | Reported effect |
|---|---|---|
| Kidney | Cell-free assays; rats with renal ischemia | Faster ATP recovery after blood flow returned |
| Skeletal muscle | Aged mice, single dose | ATP capacity and coupling back to young levels within an hour, with less H2O2 emission |
| Skeletal muscle | Aged mice, 8 weeks | ATP capacity restored; longer treadmill endurance |
| Heart | Dogs with induced heart failure, 3 months | ATP synthesis rate and ATP/ADP ratio restored |
| Hand muscle | Older adults, one infusion | Higher maximal ATP production, gone by day 7 |
The mouse and human muscle studies come from one University of Washington group with consulting ties to Stealth BioTherapeutics, the developer.
What human studies measured
We found one direct human ATP measurement. In a placebo-controlled trial published in 2021, Roshanravan and colleagues gave a single 2-hour infusion to 39 older adults with poorly functioning muscle mitochondria. Maximal ATP production in a hand muscle rose relative to placebo, but fatigue resistance did not change. Stealth funded the study.
Larger trials measured function instead. MMPOWER-3, a Phase 3 trial in 218 adults with primary mitochondrial myopathy, gave 40 mg/day subcutaneously for 24 weeks and missed both primary endpoints.
As of October 2026, elamipretide is a prescription medicine, Forzinity, for Barth syndrome (an inherited cardiolipin disorder) in patients weighing at least 30 kg. The FDA's accelerated approval on 2025-09-19 rested on knee-extensor strength, not on any ATP measure, and a confirmatory trial is required. The label dose is 40 mg subcutaneously once daily. The SS-31 overview covers the full trial record.
Performance implications
No study has tested SS-31 for ATP output or athletic performance in healthy people. The endurance results came from aged mice, and young mice showed no change. In the human study, a brief rise in ATP capacity did not reduce fatigue.
Some forum users report more energy at about 0.5-4 mg/day, far below the trial dose. Those reports are uncontrolled.
Combining with other compounds
Older guides pair SS-31 with supplements such as CoQ10 or NAD precursors. We found no study testing these combinations for ATP output.
What we still don't know
Nobody has shown whether daily dosing keeps ATP capacity raised in human muscle. The Barth approval shows a strength benefit in a cardiolipin disease, but not that ATP output improved.
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References
- Birk et al., SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin (Journal of the American Society of Nephrology, 2013)
- Siegel et al., Mitochondrial-targeted peptide rapidly improves mitochondrial energetics in aged mice (Aging Cell, 2013)
- Campbell et al., SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice (Free Radical Biology and Medicine, 2019)
- Sabbah et al., Chronic elamipretide therapy in dogs with advanced heart failure (Circulation: Heart Failure, 2016)
- Roshanravan et al., Single dose of elamipretide and mitochondrial ATP production in older adult muscle (PLoS One, 2021)
- Karaa et al., MMPOWER-3 randomized trial of elamipretide in primary mitochondrial myopathy (Neurology, 2023)
- FDA grants accelerated approval to first treatment for Barth syndrome (FDA, 2025)
- Forzinity (elamipretide) prescribing information (FDA, 2025)