Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose. We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed. The outcomes of interest were extracted using a data extraction form developed for this study. Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: -0.16; 95% CI, -0.34 to 0.01;  = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: -0.35; 95% CI,-0.61 to -0.09;  = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms. Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.