Performance research
Cellular energy, endurance, and exercise mimetics. Below is the published literature for each compound in this area — 89 studies in total, 67 of them published since 2023, every one linked to its source record.
- PerformancePreclinical only
MOTS-C
MOTS-c is a 16-amino-acid microprotein encoded within the mitochondrial 12S rRNA gene that acts as a retrograde signalling molecule, with reported effects on AMPK signalling, folate-methionine one-carbon metabolism, and nuclear stress-response gene expression. Interventional data on administered MOTS-c come almost entirely from rodent and cell-culture studies, in which the peptide improved insulin sensitivity, mitochondrial respiration and exercise capacity. Human research to date is observational or genetic: circulating MOTS-c has been measured as a candidate biomarker across metabolic, cardiovascular, renal and reproductive conditions, and a mitochondrial variant in the MOTS-c coding region (m.1382A>C, K14Q) has been associated with type 2 diabetes risk in East Asian men. No controlled clinical trial has tested exogenous MOTS-c administration in humans, so efficacy and safety in people are not established.
- Studies
- 15
- Since 2023
- 12
- Newest
- 2026
- PerformanceEarly clinical
NAD+
Nicotinamide adenine dinucleotide (NAD+) is a redox cofactor and enzyme substrate for sirtuins, PARPs and CD38, and tissue NAD+ concentrations decline with age in preclinical models. Because NAD+ itself is poorly absorbed orally, most human work has used precursors, principally nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN); randomised trials consistently show these raise circulating NAD+ two- to threefold and are well tolerated over weeks to months. Functional and clinical endpoints are far less consistent: individual trials have reported improvements in walking distance, insulin sensitivity and sleep quality, while meta-analyses of muscle, glucose and lipid outcomes have been null. Lifespan extension and stem-cell rejuvenation findings are from rodent studies and have not been demonstrated in humans.
- Studies
- 15
- Since 2023
- 11
- Newest
- 2026
- PerformanceApproved drug
PT-141
Bremelanotide (PT-141) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that acts as a non-selective agonist at melanocortin receptors, with activity at MC4R in central nervous system pathways considered central to its effects on sexual response. It was first investigated as an intranasal agent for erectile dysfunction before being redeveloped as a subcutaneous on-demand injection, and was approved by the FDA in 2019 as Vyleesi for generalised acquired hypoactive sexual desire disorder in premenopausal women. The pivotal RECONNECT phase 3 programme and its open-label extension reported statistically significant but small improvements in desire and reductions in distress, alongside high rates of nausea, flushing and headache. Independent re-analyses and subsequent systematic reviews have debated the clinical magnitude of the effect, and use in men remains investigational.
- Studies
- 15
- Since 2023
- 10
- Newest
- 2026
- PerformancePreclinical only
SLU-PP-332
SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors (ERRalpha, ERRbeta and ERRgamma), a family of orphan nuclear receptors that act with PGC-1 coactivators to regulate mitochondrial biogenesis and oxidative metabolism. Reported work characterises it as an 'exercise mimetic' because it reproduces part of the acute aerobic exercise transcriptional programme in rodent skeletal muscle, with additional published effects in mouse models of diet-induced obesity, pressure-overload heart failure and kidney ageing. The evidence base is preclinical only: it consists of rodent in vivo studies, cell-based work, medicinal-chemistry optimisation and analytical/doping-control metabolite characterisation. No human clinical trial of SLU-PP-332 has been published or registered, and no human pharmacokinetic or safety data exist.
- Studies
- 13
- Since 2023
- 13
- Newest
- 2026
- PerformanceApproved drug
SS-31
Elamipretide (SS-31, MTP-131) is a mitochondria-targeted tetrapeptide that binds cardiolipin in the inner mitochondrial membrane, stabilising cristae architecture and improving electron transport efficiency and ATP synthesis. It has been studied in randomised controlled trials in Barth syndrome, primary mitochondrial myopathy, heart failure with reduced ejection fraction, Leber hereditary optic neuropathy and ischaemia-reperfusion settings, with mixed results: the Barth syndrome programme showed sustained functional gains in a small cohort, while the phase 3 MMPOWER-3 trial in primary mitochondrial myopathy missed its primary endpoints. On 19 September 2025 the FDA granted accelerated approval to elamipretide (FORZINITY, NDA 215244, Stealth BioTherapeutics) to improve muscle strength in adult and paediatric patients with Barth syndrome weighing at least 30 kg, based on an improvement in knee extensor muscle strength; continued approval is contingent on confirmatory trials. Evidence for use in healthy individuals or for athletic performance is absent.
- Studies
- 16
- Since 2023
- 11
- Newest
- 2026
- PerformanceClinical
Superhuman Blend
The published literature relates to the individual amino acids commonly used in performance blends - glycine, glutamine, arginine, citrulline and citrulline malate, the branched-chain amino acids leucine, isoleucine and valine, beta-alanine, taurine, L-carnitine and essential amino acid mixtures - rather than to any branded combination as formulated. Human randomised trials and meta-analyses dominate this evidence base, with endpoints spanning muscle protein synthesis, high-intensity and endurance exercise performance, markers of exercise-induced muscle damage, vascular and nitric oxide-related outcomes, and fatigue. Effect sizes are generally small and heterogeneous, and several recent meta-analyses report null or very low-certainty findings for specific endpoints. No study identified evaluated the constituents together as a single fixed-ratio blend.
- Studies
- 15
- Since 2023
- 10
- Newest
- 2026
Latest published research
Circulating mitochondrial-derived microproteins at rest and in response to an acute bout of endurance exercise in individuals with cerebral palsy
Experimental Physiology · Typically developing adults, typically developing adolescents, and adults with cerebral palsy (GMFCS II-IV); acute endurance exercise bout
PubMed · 42349896MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner
Free Radical Biology and Medicine · Two transgenic mouse strains (PGC-1alpha and AMPK models) given MOTS-c; skeletal muscle mitochondrial bioenergetics
PubMed · 41520850Reduced serum and skeletal muscle MOTS c levels in women with polycystic ovary syndrome are associated with mitochondrial dysfunction
Scientific Reports · 40 women with polycystic ovary syndrome versus 40 age- and BMI-matched controls; serum and skeletal muscle sampling
PubMed · 41680431Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance
Sports Medicine · Narrative review of approved and unapproved peptides used in sports medicine, including mitochondrial-derived peptides
PubMed · 41966639Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss
Journal of Clinical & Translational Endocrinology · Cross-sectional comparison of 22 lean and 32 adults with obesity, with 10 followed after bariatric surgery weight loss
PubMed · 41551324A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment
Alzheimer's & Dementia · 12-week phase II double-blind randomised placebo-controlled pilot trial, 42 older adults with amnestic mild cognitive impairment (NR n = 22, placebo n = 20)
PubMed · 42478598Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial
Nature Medicine · single-arm open-label phase 1/2 trial, 25 adults with steroid-refractory or steroid-dependent immune thrombocytopenia, 450 mg NMN twice daily for 2 weeks, with supporting mouse macrophage experiments
PubMed · 42056497Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial
The Lancet Neurology · phase 2 single-centre 2 × 2 factorial randomised controlled trial, 66 individuals aged 10-40 with Friedreich's ataxia, 12 weeks of weight-based nicotinamide riboside (300-900 mg) and/or individualised home exercise
PubMed · 42009009
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice.