SS-31 (Elamipretide)
SS-31 (Elamipretide) is a synthetic aromatic-cationic tetrapeptide that selectively concentrates in the inner mitochondrial membrane by binding to cardiolipin, a structural phospholipid critical for cristae architecture and electron transport chain efficiency. By stabilizing cardiolipin, it reduces mitochondrial ROS production, improves ATP synthesis, and mitigates apoptotic signaling — effects demonstrated across multiple preclinical disease models. The pivotal phase 3 MMPOWER-3 trial in primary mitochondrial myopathy did not meet its primary endpoint (six-minute walk distance), though some secondary functional measures showed trends of benefit. Trials in heart failure with preserved ejection fraction (HFpEF) and other mitochondrial diseases are ongoing; no regulatory approval has been granted to date.
Evidence last reviewed: 04 Apr 2026
Not a routine supplement — not recommended for self-directed use.
Information here is educational only, not a recommendation to use. See our Safety page.
Evidence is from research or clinical settings — does not imply safety outside supervised contexts.
The evidence base includes a phase 3 trial that did not meet its primary endpoint, indicating limited efficacy in primary mitochondrial myopathy. While some secondary measures showed trends of benefit, further studies are needed to clarify its potential in other conditions.
Exercise performance (short-term, earlier phase 2 dose-escalation)Adults with primary mitochondrial myopathy · Randomized dose-escalation clinical trialModerate
An earlier short-course dose-escalation study reported improved exercise performance after 5 days; the larger phase 3 MMPOWER-3 trial did not confirm sustained benefit on primary endpoints.
Efficacy & safety — phase 3 primary endpoints not metAdults with primary mitochondrial myopathy (n=218) · Randomized, double-blind, placebo-controlled phase 3 trial (MMPOWER-3)Moderate
MMPOWER-3 found no significant improvement in 6-minute walk test distance or fatigue scores with 40 mg/day subcutaneous elamipretide vs. placebo over 24 weeks in the overall PMM population (Class I evidence of no benefit on primary endpoints). A post-hoc subgroup analysis suggested possible benefit in patients with nuclear DNA variants. Elamipretide was well-tolerated.
Mitochondria-oriented peptide grouping. SS-31 has clinical trials in specific mitochondrial diseases; MOTS-C is mostly preclinical.