APOEε4 genotype and DHA and EPA supplementation on the outcomes of cognitive decline: A systematic review of randomized clinical trials

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplementation has been used to improve cognitive outcomes in diseases associated with cognition. However, the influence of APOEε4 genotype on these relationships remains unclear. Therefore, this systematic review aims to discuss the evidence regarding the effects of DHA and EPA supplementation on cognitive decline variables and relate them to APOEε4 genotype in middle-aged and older adults. The Medline (via PubMed), Scopus, Web of Science, and Bireme/Lilacs databases were searched for studies, retrieving 1863 articles. After the step selection, two randomized clinical trials (RCTs) that evaluated the effects of EPA and DHA supplementation on cognitive variables were included. All the methodological steps were performed by two raters. The results of the RCTs were not congruent, as the non-carriers in the APOEε4 supplemented group performed worse in the quick-choice reaction time cognitive domain, whereas the carriers improved in the reasoning domain. The increase in DHA concentration in the supplemented group was lower in APOEε4 carriers than in individuals with other genotypes. Additionally, a smaller decline in right hippocampal brain volume correlated with higher EPA concentrations after supplementation in APOEε4 non-carriers. The dosage and supplementation time (18 months) were similar between studies. In conclusion, DHA and EPA supplementation showed no pragmatic effects on cognitive variables when considering the presence of the APOEε4 allele.