Editorial note: this article summarises published research on MOTS-c and SS-31 (elamipretide). Baclabs does not sell MOTS-c, SS-31 or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.
MOTS-c and SS-31 are sold together as “mitochondrial peptides”, but they are very different molecules with very different evidence. MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that behaves like an exercise signal in mice and has never been tested in a human efficacy trial. SS-31, known clinically as elamipretide, is a synthetic four-amino-acid peptide that binds the inner mitochondrial membrane, has been through a failed phase 3 trial and, in September 2025, became the first mitochondria-targeted medicine approved by the US Food and Drug Administration (FDA), for a single ultra-rare disease.
Neither has human data for fat loss, endurance or “mitochondrial health” in healthy adults. This article covers what each does, what the trials showed, the doses used, and the concentration maths for lyophilised vials.
What “mitochondrial biogenesis” means here
Two things can go wrong with mitochondria: the cell can fail to make enough of them (a biogenesis problem, governed by signals such as AMP-activated protein kinase, AMPK), or the ones it has can work inefficiently and leak reactive oxygen species (a membrane problem). MOTS-c acts mainly on the first pathway; SS-31 on the second. The marketing term flattens a real distinction.
MOTS-c: an exercise signal encoded in mitochondrial DNA
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) was identified by Changhan Lee and Pinchas Cohen’s group at the University of Southern California. In the 2015 Cell Metabolism paper, MOTS-c inhibited the folate–methionine cycle, raised intracellular AICAR and activated AMPK in skeletal muscle. Male CD-1 mice on a 60 per cent high-fat diet given 0.5 mg/kg/day by intraperitoneal injection for eight weeks were protected from obesity and insulin resistance; the same dose had no effect on weight in mice on a normal diet [1].
The 2021 Nature Communications follow-up connected the peptide to exercise. In humans, a bout of exercise raised MOTS-c in skeletal muscle 11.9-fold and in plasma 1.5-fold. In mice, 15 mg/kg/day for two weeks roughly doubled treadmill running time in old animals, and late-life intermittent treatment (15 mg/kg three times weekly) improved grip strength and gait [2].
MOTS-c mitochondrial health claims and the human evidence
The only human interventional data come from CB4211, a chemically modified MOTS-c analogue developed by CohBar. In the 2021 phase 1a/1b study, 65 healthy adults received the drug for one week (phase 1a), and 20 obese adults with fatty liver were randomised to 25 mg subcutaneously daily or placebo for four weeks (phase 1b). Alanine aminotransferase fell 21 per cent versus a 4 per cent rise on placebo, aspartate aminotransferase fell 28 per cent versus 11 per cent, and fasting glucose fell 6 per cent; body weight only trended down, and liver fat fell similarly in both arms [3]. The programme went no further. Native MOTS-c has never been given to humans in a published trial, so “MOTS-c for mitochondrial health” rests on mouse data and an analogue.
Two regulatory points follow. The World Anti-Doping Agency names MOTS-c explicitly as a prohibited AMPK activator under section S4.4.1 of the Prohibited List, banned at all times [4]. And the FDA, reviewing MOTS-c as a candidate bulk substance for pharmacy compounding, flagged a “significant risk for immunogenicity” [5]. In the UK it has no licence and is sold under research-use labelling.
SS-31 (elamipretide): from Szeto-Schiller peptides to a licensed medicine
SS-31 is the lead compound from a series of cell-permeable tetrapeptides developed by Hazel Szeto and Peter Schiller. Its alternating positive charges and aromatic rings let it concentrate in the inner mitochondrial membrane and bind cardiolipin, a phospholipid unique to that membrane; binding is proposed to stabilise cristae, improve electron transport efficiency and reduce reactive oxygen species [6].
The trials
Stealth BioTherapeutics developed elamipretide for genetic mitochondrial disease. A phase 2 crossover study in adults with primary mitochondrial myopathy gave 40 mg/day subcutaneously for four weeks and reported an improvement in six-minute walk distance [7]. The phase 3 MMPOWER-3 trial randomised participants with genetically confirmed primary mitochondrial myopathy to 40 mg/day subcutaneously or placebo for 24 weeks and failed both primary endpoints: the difference in six-minute walk distance was −3.2 m (95 per cent CI −18.7 to 12.3) and the fatigue score difference was −0.07. The authors reported Class I evidence that elamipretide does not improve walking or fatigue at 24 weeks [8].
Barth syndrome, a rare X-linked disorder of cardiolipin remodelling, was the better fit for a cardiolipin-binding drug. The TAZPOWER trial randomised 12 patients to 40 mg/day or placebo in a 12-week crossover; neither primary endpoint was met in the blinded phase, but the open-label extension showed progressive improvement in knee-extensor strength and six-minute walk distance over 168 weeks [9]. On that intermediate endpoint, and after a complete response letter in May 2025, the FDA granted accelerated approval on 19 September 2025 to Forzinity (elamipretide HCl) to improve muscle strength in adults and children with Barth syndrome weighing at least 30 kg, with continued approval contingent on a confirmatory trial [10].
SS-31 elamipretide dosage: what the licensed label and trials specify
The licensed dose is 40 mg subcutaneously once daily, reduced to 20 mg in adults with severe renal impairment. Forzinity is supplied as a ready-to-use 80 mg/mL solution in 3.5 mL vials, which are discarded eight days after first opening; no reconstitution is involved. The most common adverse reactions were injection-site reactions and a transient eosinophilia peaking around 90 days [11]. The same 40 mg/day dose was used in every trial cited above. Forzinity is not licensed in the UK or EU. Research-grade “SS-31” sold as lyophilised powder is an unlicensed product with no relationship to the pharmaceutical.
| Compound | Study | Dose in source | Route and duration | Outcome |
|---|---|---|---|---|
| MOTS-c | Lee 2015, HFD mice [1] | 0.5 mg/kg/day | Intraperitoneal, 8 weeks | Prevented obesity and insulin resistance |
| MOTS-c | Reynolds 2021, old mice [2] | 15 mg/kg, 3x weekly | Intraperitoneal, late life | Doubled running time; healthspan gains |
| CB4211 (MOTS-c analogue) | CohBar 2021, 20 obese adults [3] | 25 mg/day | Subcutaneous, 4 weeks | Lower ALT, AST, glucose; weight trend only |
| Elamipretide | MMPOWER-3, mitochondrial myopathy [8] | 40 mg/day | Subcutaneous, 24 weeks | Primary endpoints not met |
| Elamipretide | TAZPOWER, Barth syndrome [9] | 40 mg/day | Subcutaneous, 12 weeks + extension | Strength gains in open-label phase |
| Elamipretide (Forzinity) | US label, Barth syndrome [11] | 40 mg once daily | Subcutaneous, ongoing | Licensed dose |
Reconstitution maths for MOTS-c and SS-31
Research-grade MOTS-c is usually supplied in 10 mg lyophilised vials and SS-31 in 10 mg or 50 mg vials. The concentration after reconstitution is:
Concentration (mg/mL) = vial content (mg) ÷ diluent volume (mL). On a U-100 insulin syringe each unit is 0.01 mL, so mcg per unit = concentration in mg/mL × 10.
Worked example: 10 mg MOTS-c + 2 mL bacteriostatic water = 5 mg/mL = 5,000 mcg/mL, so each unit holds 50 mcg and 20 units hold 1 mg.
| Vial | Diluent added | Concentration | mcg per U-100 unit | Units for 1 mg | Units for 5 mg |
|---|---|---|---|---|---|
| MOTS-c 10 mg | 1 mL | 10 mg/mL | 100 | 10 | 50 |
| MOTS-c 10 mg | 2 mL | 5 mg/mL | 50 | 20 | 100 |
| MOTS-c 10 mg | 3 mL | 3.33 mg/mL | 33.3 | 30 | 150 |
| SS-31 10 mg | 1 mL | 10 mg/mL | 100 | 10 | 50 |
| SS-31 50 mg | 2 mL | 25 mg/mL | 250 | 4 | 20 |
| SS-31 50 mg | 5 mL | 10 mg/mL | 100 | 10 | 50 |
A vial drawn from more than once needs a preserved diluent. Bacteriostatic water contains 0.9 per cent benzyl alcohol and is suitable for multi-dose use for up to 28 days after first puncture; sterile water has no preservative. See bacteriostatic water vs sterile water for the comparison and bacteriostatic water storage and shelf life for the 28-day rule. Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials; the reconstitution guide has the full method.
Within the metabolic peptides group, MOTS-c sits with the rodent-only compounds and SS-31 stands alone as a licensed medicine with a narrow indication. AICAR, covered in the SLU-332, AICAR and 5-Amino-1MQ article, works on the same AMPK pathway and carries the same WADA prohibition.
Frequently asked questions
What does MOTS-c do for mitochondrial health?
In mice, MOTS-c activates AMPK in skeletal muscle, improves insulin sensitivity on a high-fat diet and roughly doubles treadmill endurance in old animals. In humans, endogenous MOTS-c rises with exercise. No trial has given native MOTS-c to people, so claims about human mitochondrial health are extrapolation from animal work and one small trial of an analogue.
What is the SS-31 elamipretide dosage in trials?
Every major trial, and the licensed US label for Barth syndrome, used 40 mg subcutaneously once daily, reduced to 20 mg in severe renal impairment. The pharmaceutical is a ready-to-use 80 mg/mL solution. Research-grade SS-31 sold as powder has no trial-based dose because it has never been studied in that form.
Is SS-31 approved in the UK?
No. Forzinity (elamipretide) has US accelerated approval, granted in September 2025, for muscle strength in Barth syndrome only. It has no UK or EU marketing authorisation, and it is not approved anywhere for fat loss, ageing, endurance or general mitochondrial support.
Is MOTS-c banned in sport?
Yes. The WADA Prohibited List names MOTS-c alongside AICAR as an AMPK activator under section S4.4.1, prohibited at all times in and out of competition. Tested athletes should treat it as a doping violation risk regardless of how it is labelled.
References
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee et al., Cell Metabolism, 2015
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds et al., Nature Communications, 2021
- CohBar announces positive topline results from the phase 1a/1b study of CB4211. GlobeNewswire, 2021
- The Prohibited List, section S4.4.1 (AMPK activators). World Anti-Doping Agency, 2026
- Certain bulk drug substances for use in compounding that may present significant safety risks. US Food and Drug Administration, 2025
- Elamipretide: a review of its structure, mechanism of action, and therapeutic potential. Tung et al., International Journal of Molecular Sciences, 2025
- A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. Karaa et al., Journal of Cachexia, Sarcopenia and Muscle, 2020
- Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Karaa et al., Neurology, 2023
- A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Thompson et al., Genetics in Medicine, 2021
- Stealth BioTherapeutics announces FDA accelerated approval of Forzinity (elamipretide HCl). PR Newswire, 2025
- Forzinity (elamipretide hydrochloride) injection: prescribing information. DailyMed, US National Library of Medicine, 2025
Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.