Abstract
The dose-dependent effects of omega-3 supplementation on cognitive function remain unclear. This study aimed to evaluate the relationship between omega-3 dosage and cognitive outcomes in adults. A systematic search was conducted in PubMed, Scopus, and ISI Web of Science up to December 2024. Only randomized controlled trials (RCTs) were included. For each trial, we estimated the change in cognitive function per 2000 mg/day increment in omega-3 supplementation. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-dependent effects were assessed through a dose-response meta-analysis of mean differences. The certainty of the evidence was evaluated using the GRADE approach. In total, 58 studies met the inclusion criteria. Each 2000 mg/d omega-3 supplementation showed a significant improvement in attention (SMD: 0.98; 95%CI: 0.41,1.54; GRADE = low), perceptual speed (SMD: 0.50; 95%CI: 0.05,0.95; GRADE = moderate) language (SMD: 0.98; 95%CI: 0.41,1.54; GRADE = low), primary memory (SMD: 0.87; 95%CI: 0.17,1.56; GRADE = moderate), visuospatial functions (SMD: 0.86; 95%CI: 0.46,1.27; GRADE = moderate), global cognitive abilities (SMD: 1.08; 95%CI: 0.73,1.44; GRADE = low). Levels of episodic memory decreased with the increase in omega-3 dose and then appeared to increase with an upward curve (P for non-linearity = 0.01, P for dose-response = 0.005). Levels of global cognitive abilities increased with the increase in omega-3 dosage, and then appeared to decreased with a downward curve (P for non-linearity = 0.008, P for dose-response = 0.002). The existing evidence suggests that omega-3 supplementation may lead to a modest improvement in cognitive function among adults. However, well-designed randomized trials with long-term follow-up are necessary to confirm and strengthen these findings.