Creatine and cognitive function in rodents: A systematic review of behavioral and neurobiological evidence.
Level 5 - mechanism / opinion, no new human data
Systematic review of preclinical animal (rodent) experiments.
PubMed 42331064 · doi:10.1016/j.bbr.2026.116340
What was done
Authors conducted a systematic review following PRISMA 2020 guidelines, searching Scopus, PubMed, and Web of Science for experimental studies published between 2015 and 2026. Studies assessing creatine supplementation on cognitive performance and behavioral or neurobiological outcomes in rodent models (healthy, neurodegeneration, metabolic insult, perinatal stress, or creatine biosynthesis deficiency) were included. Risk of bias was assessed using SYRCLE's tool. A total of 19 rodent studies were included.
What was found
No quantitative effect sizes or numerical statistics were reported in the abstract. Creatine improved learning and memory in the majority of the 19 studies. Effects were moderated by administration route (intranasal showed greater brain uptake and cognitive effects compared to oral), treatment duration, and sex. Reported mechanisms included enhanced mitochondrial respiratory capacity, upregulation of synaptic plasticity proteins (CaMKII, PSD-95, BDNF) via CaMKII/CREB and PI3K/AKT/mTOR signaling, attenuation of neuroinflammation via NF-κB suppression and STAT1 inhibition, and decreased oxidative stress through CK-BB restoration.
Why it matters
This review maps preclinical evidence on how creatine may enhance cognition beyond energy metabolism and highlights route of administration (such as intranasal delivery) as a key moderator for brain bioavailability.
Limits
The findings are strictly restricted to rodent models, limiting direct translation to humans. The abstract omits numerical effect sizes, meta-analytic pooling, and specific results of the SYRCLE risk-of-bias assessments.
Cited by
- supports Creatine supplementation has been shown in animal models to increase levels of brain-derived neurotrophic factor (BDNF).