Omega-6 to Omega-3 Fatty Acid Ratio in Patients with ADHD: A Meta-Analysis.

OBJECTIVE Omega-3 and omega-6 fatty acids have been shown to be deficient in individuals with attention deficit/hyperactivity disorder compared to controls (Hawkey & Nigg, 2014). Clinical trials of omega-3 and omega-6 supplements as treatment for ADHD have demonstrated minimal efficacy (Bloch & Qawasmi, 2011; Gillies, Sinn, Lad, Leach, & Ross, 2011; Hawkey & Nigg, 2014; Puri & Martins, 2014; Sonuga-Barke et al., 2013). Existing trials have analyzed omega-3 and omega-6 separately although the tissue ratio of these fatty acids (n6/n3) may be more important than absolute levels of either. The objective of this study was to determine the relationship between blood n6/n3 and arachidonic acid to eicosapentaenoic acid (AA/EPA), to ADHD symptoms. METHOD A systematic literature review identified original articles measuring blood n6/n3 or AA/EPA ratio in children and youth with ADHD, compared to controls without ADHD. Three databases were searched. Blood n6/n3, and AA/EPA ratios were compared between individuals with ADHD and controls. Results were pooled across studies using quantitative synthesis. RESULTS Five articles met inclusion criteria for the meta-analysis. The pooled mean difference between patients with ADHD and controls was 1.97 (0.90-3.04) for n6/n3 (n=5 studies, I(2) 83%) and 8.25 (5.94-10.56) for AA/EPA (n=3 studies, I(2) 0%). CONCLUSIONS Children and youth with ADHD have elevated ratios of both blood n6/n3 and AA/EPA fatty acids compared to controls. Thus an elevated n6/n3, and more specifically AA/EPA, ratio may represent the underlying disturbance in essential fatty acid levels in patients with ADHD. These findings have implications for the development of future interventions using essential fatty acids to treat ADHD, and for the use of these ratios as biomarkers for titrating and monitoring ADHD treatment with essential fatty acids.