Comparison · Updated
MOTS-c VS SS-31
Short answer
SS-31 has stronger published evidence than MOTS-c: tier S (Approved) vs tier C (Animal data).
MOTS-c is not FDA-approved; SS-31 is FDA-approved (Forzinity, 2025).
MOTS-c is prohibited in sport by WADA under section S4; SS-31 is not on the WADA Prohibited List.
01
Side by side
| Field | MOTS-c | SS-31 |
|---|---|---|
| Evidence tier | C Tier C · Animal data | S Tier S · Approved |
| Tier rationale | Interventional evidence is from rodent studies (e.g. Lee et al., Cell Metab 2015); human data are observational measurements of circulating levels, with no published human trial of MOTS-c itself. | FDA granted accelerated approval in September 2025 (Forzinity) to improve muscle strength in Barth syndrome. Continued approval depends on a confirmatory randomized trial. |
| FDA status | Not approved | Approved (2025) ForzinityAccelerated approval to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg. |
| Other approvals | None listed | None listed |
| WADA | Prohibited · S4Hormone and metabolic modulators | Not on the Prohibited List |
| Family | Metabolic | Longevity & Immune |
| Residues | 16amino acids | 4amino acids |
| Molecular weight | 2,174.6 Da | 639.8 Da |
| Formula | C101H152N28O22S2 | C32H49N9O5 |
| Discovered | 2015Identified as a peptide encoded in the mitochondrial 12S rRNA gene (Lee et al., Cell Metab 2015). | Not on file |
| Routes studied | Subcutaneous, Intramuscular | Subcutaneous, Intramuscular |
| Mechanism | MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial 12S rRNA gene. It translocates to the nucleus during metabolic stress and activates AMPK signaling, which promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. | SS-31 (Elamipretide) is a cell-permeable aromatic-cationic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that concentrates 1000-fold in the inner mitochondrial membrane. It binds cardiolipin, stabilizing its interaction with cytochrome c and restoring electron transport chain efficiency. |
| Safety notes | Endogenous mitochondrial-derived peptide with naturally declining levels during aging. | FDA-approved (Forzinity, accelerated approval 2025) for Barth syndrome; continued approval depends on a confirmatory randomized trial. |
| Cited studies | 1 study | 2 studies |
02
Questions
- Which has stronger evidence, MOTS-c or SS-31?
- SS-31 has stronger published evidence than MOTS-c: tier S (Approved) vs tier C (Animal data). MOTS-c: Interventional evidence is from rodent studies (e.g. Lee et al., Cell Metab 2015); human data are observational measurements of circulating levels, with no published human trial of MOTS-c itself. SS-31: FDA granted accelerated approval in September 2025 (Forzinity) to improve muscle strength in Barth syndrome. Continued approval depends on a confirmatory randomized trial. Tiers rate the strength of published evidence, not effectiveness.
- Is MOTS-c FDA-approved?
- MOTS-c is not FDA-approved.
- Is SS-31 FDA-approved?
- SS-31 is FDA-approved (Forzinity, 2025). Accelerated approval to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg.
- Are MOTS-c and SS-31 banned in sport?
- MOTS-c is prohibited in sport by WADA under section S4; SS-31 is not on the WADA Prohibited List.
- How do MOTS-c and SS-31 work?
- MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial 12S rRNA gene. SS-31 (Elamipretide) is a cell-permeable aromatic-cationic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that concentrates 1000-fold in the inner mitochondrial membrane.