The More, the Better: High-Dose Omega-3 Fatty Acids Improve Behavioural and Molecular Outcomes in Preclinical Models in Mild Brain Injury.

Preclinical studies using rodent models are key to understanding molecular mechanisms underlying improvements post-injury. Studies to date have shown improved outcomes in rodent models following mTBI protocols, but these data have not been quantified using a systematic review and meta-analysis approach. Our systematic review assessed 291 studies identified from the literature. Of these studies, 18 studies met inclusion criteria. We conducted a meta-analysis examining the effect of high-dose n-3FA vs placebo on neurological, cognitive and molecular changes following mTBI. Quality of studies was rated as moderate to high quality, and while mostly compliant, some areas of risk of bias were identified. Results showed that preclinical doses of 10-370 mg/kg/day of n-3FA per day in rodents (equivalent to high clinical doses) resulted in improvements in neurological and cognitive performance (pooled effect sizes ranging between 1.52 and 3.55). Similarly, improvements in molecular and inflammatory markers were observed in treated rodents vs control (pooled effect sizes: 3.73-6.55). Overall, these findings highlight the potential for high-dose n-3FA for human clinical studies following mTBI.