MOTS-c vs SS-31
Both target mitochondria, the cell’s power plants, in different ways, and both are sold for energy and healthy aging. SS-31 (elamipretide) was approved in 2025 as Forzinity for a rare mitochondrial disease; native MOTS-c has never been tested in people.
- MOTS-c
- Preclinical1–3× per week
- SS-31
- Approved drugOnce daily
- Head-to-head trials
- None published
The short answer
MOTS-c is a 16-amino-acid peptide the body makes from mitochondrial DNA. It acts as a signal to the rest of the cell: in cells and mice it switches on AMPK, an enzyme that responds when energy runs low. SS-31 (elamipretide) is a four-amino-acid peptide designed in a lab that collects in the inner membrane of mitochondria and binds cardiolipin, a fat that holds that membrane’s folds in shape. SS-31 is an approved drug for one rare disease; MOTS-c isn’t approved and has only animal data.
On September 19, 2025, FDA granted elamipretide accelerated approval as Forzinity, a 40 mg daily injection to improve muscle strength in Barth syndrome, an inherited mitochondrial disease, in patients weighing at least 30 kg; keeping that approval depends on a confirmatory trial. The approval rests on 12 patients: the randomized part of their trial missed its walking and fatigue goals, and knee strength rose only in the open-label extension. Larger trials in mitochondrial myopathy and heart failure showed no benefit. Native MOTS-c has never been tested in a published human study; a modified version, CB4211, finished a small Phase 1b trial.
At a glance
| Field | MOTS-cMitochondrial open reading frame of the 12S rRNA-c | SS-31Elamipretide (Forzinity) |
|---|---|---|
| Evidence | Preclinical | Approved drug |
| Class | Mitochondrial-derived peptide | Mitochondria-targeted peptide |
| Approval | Not approved as a drug in the US or EU. | Approved in the US in 2025 as Forzinity (accelerated approval), to improve muscle strength in Barth syndrome patients weighing at least 30 kg. |
| Sport (WADA 2026) | Banned in sport | Not banned in sport |
| Common dose | 5 mg, 1–3× weekly | Label 40 mg; community 1–10 mg daily |
| Frequency | 1–3× per week | Once daily |
| Cycle | 8 weeks on, 4 off | 8 weeks on, 4 off |
| Route | Subcutaneous injection | Subcutaneous injection |
| Half-life | – | – |
| Typical draw | 50 units10 mg with 1 mL, 5 mg | 50 units10 mg with 1 mL, 5 mg |
| Vial sizes or form | 10, 20, 40 mg | 10, 50 mg |
| Human studies | None found | 5 listedLargest: 218 people (2023) |
| Main cautions |
|
|
| Open MOTS-c | Open SS-31 |
Doses shown are what labels, trials or community reports reference, not recommendations. Each compound’s page has the full detail and sources.
Key differences
What they are
MOTS-c: 16 amino acids (MRWQEMGYIFYPRKLR), encoded in mitochondrial DNA and made naturally in the body. SS-31: 4 amino acids, D-arginine, dimethyltyrosine, lysine and phenylalanine, designed in a lab.
How they work
MOTS-c is a messenger: in cells and mice it switches on AMPK and, under metabolic stress, moves into the nucleus to change which genes are read. SS-31 stays at the inner mitochondrial membrane and binds cardiolipin; Forzinity’s label says this improves mitochondrial shape and function.
Human evidence
TrialSS-31: placebo-controlled trials in Barth syndrome (12 people), primary mitochondrial myopathy, an inherited muscle disease (218, missed its goals), heart failure (71, no improvement on heart scans) and healthy older adults (39, one IV dose), plus the open-label extension behind its approval. MOTS-c: none for the native peptide; its analog CB4211 went through a Phase 1 program of 88 people, with no journal report.
Doses
SS-31: 40 mg under the skin once a day for Barth syndrome; the label lowers it to 20 mg for adults with severe kidney impairment who aren’t on dialysis. Community use is 1–10 mg a day, with no trial support. MOTS-c: 5 mg, 1–3 times a week, up to 10 mg per injection (community).
Side effects
SS-31: injection-site reactions in nearly everyone in the Barth syndrome trial (redness 100% vs 25% on placebo, pain 75% vs 42%), a rise in eosinophils, a type of white blood cell, peaking around day 90, and a label warning for serious allergic reactions. MOTS-c: injection-site reactions were the main side effect of its analog; low blood sugar is a theoretical risk.
Status
SS-31: FDA accelerated approval in 2025 as Forzinity. MOTS-c: not approved; its compounding nomination was withdrawn, and in July 2026 FDA’s advisory committee voted 7 to 5 to recommend adding it to the pharmacy compounding list.
In sport
MOTS-c is banned at all times: WADA’s 2026 list names it under S4.4.1 as an AMPK activator. SS-31 isn’t named, and as an approved drug it falls outside the S0 rule for unapproved substances.
Head-to-head studies
Taking them together
Their pages list them as a common pairing. That reflects community practice, not trials.
The usual ‘mito stack’ pairing: SS-31 protects the mitochondrial membrane, MOTS-c boosts energy signaling. No human data on the combination.
Open them in the stack check for sport status and one combined tracking checklist.
Questions
What is the difference between MOTS-c and SS-31?
MOTS-c is a 16-amino-acid peptide the body makes from mitochondrial DNA. It acts as a signal to the rest of the cell: in cells and mice it switches on AMPK, an enzyme that responds when energy runs low. SS-31 (elamipretide) is a four-amino-acid peptide designed in a lab that collects in the inner membrane of mitochondria and binds cardiolipin, a fat that holds that membrane’s folds in shape. SS-31 is an approved drug for one rare disease; MOTS-c isn’t approved and has only animal data.
Is SS-31 the same as elamipretide?
Yes. SS-31 is the research code for elamipretide, the active ingredient in Forzinity. Forzinity is a ready-made 80 mg/mL solution approved for Barth syndrome; vials sold as SS-31 for research are powders made outside that approval.
Does Forzinity’s approval mean SS-31 works for energy or aging?
No. The approval covers muscle strength in Barth syndrome, a rare inherited disease, and rests on knee-strength gains in 8 to 10 patients during an open-label extension; continued approval depends on a confirmatory trial. In 218 adults with primary mitochondrial myopathy, 40 mg a day didn’t improve walking distance or fatigue over 24 weeks. In 39 healthy older adults, one IV dose briefly raised a hand muscle’s capacity to make energy but didn’t reduce its fatigue, and the rise was gone a week later.
Can MOTS-c and SS-31 be taken together?
No overlap is documented. They’re a common pairing in community practice: the usual ‘mito stack’ pairing: SS-31 protects the mitochondrial membrane, MOTS-c boosts energy signaling. No human data on the combination. No published study has tested them together.
Which has more evidence in people, MOTS-c or SS-31?
MOTS-c isn’t approved anywhere and rests mainly on cell and animal studies; its page lists no published human studies. SS-31 is approved in the US; its page lists 5 key human studies. They haven’t been compared directly in a published trial.
Are MOTS-c and SS-31 banned in sport?
MOTS-c is banned at all times. SS-31 isn’t banned. This follows the WADA 2026 Prohibited List; athletes should confirm with their anti-doping organization.
Sources
- Forzinity (elamipretide) prescribing information (DailyMed, December 2025)
- Drugs@FDA: Forzinity, NDA 215244, accelerated approval September 19, 2025
- Thompson et al., elamipretide in Barth syndrome, 168-week open-label extension of TAZPOWER (Genet Med 2024) PMID 38602181
- Karaa et al., elamipretide in primary mitochondrial myopathy, MMPOWER-3 (Neurology 2023) PMID 37268435
- Roshanravan et al., one dose of elamipretide in older adults’ muscle (PLoS One 2021) PMID 34264994
- Lee et al., MOTS-c promotes metabolic homeostasis (Cell Metab 2015) PMID 25738459
- Phase 1a/1b trial of the MOTS-c analog CB4211: ClinicalTrials.gov registry entry NCT03998514
- WADA 2026 Prohibited List, in force January 1, 2026