SS-31 Weight Gain

Body weight in animal studies: no change measured

The most direct data on this question come from mice. In C57BL/6 mice fed a high-fat diet for 28 weeks, SS-31 had no effect on weight gain, insulin resistance or hyperglycemia. The kidneys of the same animals did differ. Mitochondrial structure stayed normal in glomerular and tubular cells, and intracellular lipid accumulation, endoplasmic reticulum stress and apoptosis were all lower than in high-fat controls. The kidney endpoints changed. Body weight did not.Animal study · PMID 27519664

Pigs show the same pattern. In a study of 18 domestic pigs (6 per group), animals fed a metabolic-syndrome diet for 16 weeks and given elamipretide during the final 4 weeks developed obesity, hyperlipidemia, insulin resistance and hypertension similar to pigs given vehicle. Coronary endothelial mitochondrial density fell in the diet-only pigs but was at lean-control levels in the elamipretide group. Myocardial perfusion did not differ between groups. A related pig study using the same 16-week diet reported restored kidney autophagy proteins and less renal fibrosis, and its abstract gives no body-weight figures.Animal study · PMID 29196345Animal study · PMID 36139466

Other metabolic animal work did not report body weight at all. In rats on a high-fat diet, a mitochondria-targeted antioxidant kept insulin sensitivity intact, though the abstract does not name the compound. In diabetic TallyHO mice given SS31 for 4 weeks, mitochondrial H2O2 production, lipid peroxidation and ATP production returned close to normal. Neither abstract reports weight.Animal study · PMID 19188683Animal study · PMID 33025510

Muscle size: the closest thing to a gain signal

One rat study measured tissue mass in a way searchers may care about: muscle fiber size. Female ZSF1 rats with heart failure with preserved ejection fraction (HFpEF) were randomized at 20 weeks of age to saline (n=12) or elamipretide (n=12) for 12 weeks, and 10 lean rats served as controls. In the saline-given HFpEF rats, muscle cardiolipin was 6.8% below lean-control levels and fibers showed atrophy. In the elamipretide group, fiber size was 49% larger in the soleus and 54.8% larger in the extensor digitorum longus than in the saline group. Whole-muscle force was 8.2% and 10.9% higher, respectively.Animal study · PMID 42290373

This finding is about muscle fibers in a disease model. It is not about body weight in healthy animals or people. A companion study in the same obese rat model found that 12 weeks of elamipretide raised cardiac complex I and II respiration only modestly. Diastolic dysfunction persisted, and hypertrophy and fibrosis were unaltered. Ejection fraction fell slightly. Mitochondrial readouts in rodents do not always line up with whole-organ or whole-body changes.Animal study · PMID 41596703

What the human trials measured

The largest human study is MMPOWER-3, a 24-week randomized, placebo-controlled trial of 218 adults with primary mitochondrial myopathy (mean age 45.6 years, 64% women). The study missed both primary endpoints. The difference in 6-minute walk distance versus placebo was -3.2 meters (p = 0.69), and the fatigue score difference was -0.07 (p = 0.37). The abstract reports no body-weight data.Human RCT · PMID 37268435

Earlier, smaller trials pointed the same way. In a randomized trial of 36 adults with mitochondrial myopathy, the highest-exposure group walked 64.5 meters farther at day 5, compared with 20.4 meters on placebo (p = 0.053). In MMPOWER-2, a crossover trial of 30 adults with 4-week periods, the walk distance difference was 19.8 meters (p = 0.083). Self-reported fatigue was lower than on placebo (p = 0.0006).Human RCT · PMID 29500292Human RCT · PMID 32096613

Barth syndrome is relevant to weight because its features include growth abnormalities. In TAZPOWER, 12 participants were randomized in a crossover design, and neither primary endpoint was met in part 1. In the open-label extension, walk distance rose by 95.9 meters at 36 weeks, and 8 participants reached week 168 with a cumulative gain of 96.1 meters. Neither abstract reports body weight or growth.Human RCT · PMID 37041653Human RCT · PMID 33077895Human RCT · PMID 38602181

Reported adverse events and blood pressure

In MMPOWER-2, local skin reactions at the site where the compound was given were the most common adverse event, reported by 80% of participants. Most were mild, and no serious adverse events or deaths occurred. In MMPOWER-3, most adverse events were mild to moderate. Local site reactions were also the most common events across the 168-week Barth syndrome extension. None of these abstracts lists weight change as an adverse event.Human RCT · PMID 32096613Human RCT · PMID 37268435Human RCT · PMID 38602181

In a randomized trial of 36 adults with heart failure with reduced ejection fraction, each given a single four-hour exposure, blood pressure and heart rate stayed stable in every group. No serious adverse events occurred. In the highest-exposure group, left ventricular end-diastolic volume fell by 18 compared with placebo. In a pilot trial of 14 adults undergoing renal artery stenting, systolic blood pressure fell more over 3 months in the elamipretide group than in the placebo group.Human RCT · PMID 29217757Human RCT · PMID 28916603

Why SS-31 research centers on mitochondria, not body mass

SS-31, also called elamipretide, MTP-131 and Bendavia, is an aromatic-cationic tetrapeptide. It enters cells, localizes to the inner mitochondrial membrane and binds cardiolipin. Reviews describe it as stabilizing cristae structure and reducing oxidative stress. It is not a hormone and does not belong to the growth hormone family.Human RCT · PMID 29500292Review · PMID 39940712

Most of the preclinical results are tissue-level. In cultured podocytes exposed to high glucose, SS-31 reduced mitochondrial dysfunction and cell injury. In rabbits, infarct size was about 50% smaller when the peptide was present before reperfusion, yet it showed no ROS-scavenging activity in cell-free systems. In rats after myocardial infarction, ejection fraction was 55.3% versus 49.3% in controls at 6 weeks.In vitro · PMID 38200543Animal study · PMID 24288396Animal study · PMID 25165999

The evidence on SS-31 and weight gain is thin and comes only from animals. It consists of one mouse study and one pig study, and both found no change. Human data on body weight are absent. Any compound's research value depends on what is actually in the vial, which is why batch testing matters.Animal study · PMID 27519664Animal study · PMID 29196345

The studies at a glance

Selected SS-31 (elamipretide) studies and what they measured

Frequently asked questions