MOTS-c vs SS-31

Side by side

MOTS-c Low and SS-31 High are both marketed for energy, endurance and ageing because they relate to mitochondria. They act in different ways and sit at opposite ends of the evidence scale ¹. The table is read from our encyclopedia entries.

SS-31: an approved drug for a rare disease

SS-31, elamipretide, is a synthetic peptide that binds cardiolipin, a lipid of the inner mitochondrial membrane (animal and laboratory study) ². FDA granted it accelerated approval on September 19, 2025 as Forzinity, for improvement of muscle strength in adults and children with Barth syndrome weighing at least 30 kg ¹. That approval rests on a small programme: a randomised crossover trial in 12 people with Barth syndrome, whose crossover portion did not meet its primary endpoint but whose open-label extension showed improvements in walking distance, strength and fatigue (randomised trial and extension) ³, summarised in a 2025 review of the development programme (review) ⁴. Accelerated approval means further evidence of clinical benefit can be required.

Outside Barth syndrome, results have been disappointing. In a phase 3 trial of 218 adults with primary mitochondrial myopathy, it did not improve the six-minute walk or fatigue scores at 24 weeks against placebo (randomised trial) ⁵; a 48-week trial in dry age-related macular degeneration missed its primary endpoints, though a secondary measure of photoreceptor integrity favoured it, and injection-site reactions led 17% to stop against about 9% on placebo (randomised trial) ⁶; and in a phase 2 trial of 71 people with heart failure, the primary heart-volume measure did not differ from placebo at either dose (randomised trial) ⁷.

MOTS-c: a mitochondrial-DNA peptide studied in mice

MOTS-c is a 16-amino-acid peptide encoded inside the mitochondrial genome, named in 2015 in work showing it regulates insulin sensitivity and metabolism, mainly in muscle (animal study) ⁸. In mice it enhanced physical performance at young, middle and old ages, and intermittent treatment started late in life improved physical capacity (animal study) ⁹. It is not approved for any use ¹.

Human evidence is observational. A variant of MOTS-c found in East Asian populations was associated with more type 2 diabetes in men in a meta-analysis of 27,527 people (genetic association) ¹⁰, and blood levels rose with exercise in some groups of breast-cancer survivors in a trial of exercise, not of MOTS-c (human study) ¹¹. No trial has given MOTS-c to people as a treatment.

Why 'mitochondrial peptide' hides big differences

SS-31 is a designed drug that targets a membrane lipid inside mitochondria; MOTS-c is a natural signal that travels to the nucleus under stress and changes gene expression ^{2 8}. SS-31 has been tested in hundreds of patients and approved for one rare disease after mixed results elsewhere; MOTS-c has not been tested as a treatment in people at all. The shared label tells you little about either.

Questions to ask before choosing either

• Do I have Barth syndrome or another condition SS-31 has been tested in? Outside Barth syndrome, its trials mostly missed their goals ^{5 7}.
• Is the SS-31 on offer the approved Forzinity product, prescribed, or a research powder?
• Has MOTS-c ever been given to people as a treatment in a published trial? As of October 3, 2026, we found none.
• Am I an athlete? MOTS-c is named on the WADA list ¹.

How the differences add up (as of October 3, 2026)

On human evidence, SS-31 is far ahead, with an FDA accelerated approval for Barth syndrome and phase 3 trials, though most outside that disease missed their goals. MOTS-c remains a promising animal-stage compound. For athletes the difference is sharp: WADA names MOTS-c under S4.4.1 as a metabolic modulator, while SS-31 is not listed ¹. Doses on this page are those in our entries' sources, not recommendations.

Frequently asked questions

What is the difference between MOTS-c and SS-31?

SS-31 (elamipretide) is a designed peptide that binds cardiolipin in mitochondria and is FDA-approved for Barth syndrome; MOTS-c is a natural peptide encoded in mitochondrial DNA, studied mainly in mice.

Is SS-31 FDA-approved?

Yes, as Forzinity, under accelerated approval on September 19, 2025, for muscle strength in Barth syndrome patients weighing at least 30 kg.

Is MOTS-c banned in sport?

Yes. WADA names MOTS-c under S4.4.1, metabolic modulators. SS-31 is not listed.

Related on Grey Peptides

• MOTS-c
• SS-31 (elamipretide)
• WADA hub

Sources

1. Grey Peptides dataset records for MOTS-c and SS-31 (elamipretide): FDA status (Forzinity accelerated approval for Barth syndrome, September 19, 2025), WADA status (MOTS-c S4.4.1 named; SS-31 not listed), studied doses as sourced on each entry; read October 3, 2026.
2. Birk, A. V., et al. (2013). The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol, 24(8), 1250-61. PMID: 23813215
3. Reid Thompson, W., et al. (2021). A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genet Med, 23(3), 471-478. PMID: 33077895
4. Shirley, M. (2026). Elamipretide: First Approval. Drugs, 86(3), 377-383. PMID: 41335372
5. Karaa, A., et al. (2023). Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology, 101(3), e238-e252. PMID: 37268435
6. Ehlers, J. P., et al. (2025). ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. Ophthalmol Sci, 5(1), 100628. PMID: 39605874
7. Butler, J., et al. (2020). Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. J Card Fail, 26(5), 429-437. PMID: 32068002
8. Lee, C., et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 21(3), 443-54. PMID: 25738459
9. Reynolds, J. C., et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun, 12(1), 470. PMID: 33473109
10. Zempo, H., et al. (2021). A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY), 13(2), 1692-1717. PMID: 33468709
11. Dieli-Conwright, C. M., et al. (2021). Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Sci Rep, 11(1), 16916. PMID: 34413391

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose.