Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder: a Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies

Abstract

The role of omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) in the pathogenesis and treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD) is unclear. A systematic review followed by meta-analysis was conducted on: (1) randomized controlled trials (RCTs) assessing the effects of n-3 PUFAs on clinical symptoms and cognition in children and adolescent with ADHD; and (2) case-control studies assessing the levels of n-3 PUFAs in blood and buccal tissues of children and adolescents with ADHD. In seven RCTs, totalling n=534 randomized youth with ADHD, n-3 PUFAs supplementation improves ADHD clinical symptom scores (g=0.38, p<0.0001); and in three RCTs, totalling n=214 randomized youth with ADHD, n-3 PUFAs supplementation improves cognitive measures associated with attention (g=1.09, p=0.001). Moreover, children and adolescents with ADHD have lower levels of DHA (seven studies, n=412, g=-0.76, p=0.0002), EPA (seven studies, n=468, g=-0.38, p=0.0008), and total n-3 PUFAs (six studies, n=396, g=-0.58, p=0.0001). In summary, there is evidence that n-3 PUFAs supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD, and that these youth have a deficiency in n-3 PUFAs levels. Our findings provide further support to the rationale for using n-3 PUFAs as a treatment option for ADHD.

Figures

Figure 1

PRISMA Flow Diagram. AA, arachidonic acid; BM, backward memory; Cog, cognition, Com, commission errors; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FM, forward memory; HI, hyperactivity-impulsivity; IA, inattention; IP, information processing; N-3, omega-3; N-6, omega-6; Om, omission errors.

Figure 2

Forest plots showing effect sizes (Hedges’s g) and 95% confidence intervals (CIs) from individual studies and pooled results comparing ADHD clinical symptoms, (a) inattention symptom scores, (b) hyperactivity symptom scores, (c) total ADHD symptom scores, between n3 and placebo group. ADHD, attention deficit hyperactivity disorder; CI, confidence interval; Std, standard; EPA, eicosapentaenoic acids; DHA, docosahexaenoic acids; N3, n-3 or omega-3 polyunsaturated fatty acids; >=500, clinical trials with EPA dosage > 500mg; <500, clinical trials with EPA dosage <500mg.

Figure 3

Forest plots showing effect sizes (Hedges’s g) and 95% confidence intervals (CIs) from individual studies and pooled results comparing cognitive function, (a) omission and (b) commission, between n-3 group and placebo group. CI, confidence interval; N3, n-3 or omega-3 polyunsaturated fatty acid; Std, standard.

Figure 4

Forest plots showing effect sizes (Hedges’s g) and 95% confidence intervals (CIs) from individual studies and pooled results comparing n-3 PUFAs Levels, (a) DHA, (b) EPA, (c) n-3, (d) AA, (e) n-6, between ADHD population and control group. AA, arachidonic acids; ADHD, attention deficit hyperactivity disorder; CI, confidence interval; DHA, docosahexaenoic acids; EPA, eicosapentaenoic acids; N3, n-3 or omega-3 polyunsaturated fatty acids; N6, n-6 or omega-6 polyunsaturated fatty acids; Std, standard.

Figure 4

Forest plots showing effect sizes (Hedges’s g) and 95% confidence intervals (CIs) from individual studies and pooled results comparing n-3 PUFAs Levels, (a) DHA, (b) EPA, (c) n-3, (d) AA, (e) n-6, between ADHD population and control group. AA, arachidonic acids; ADHD, attention deficit hyperactivity disorder; CI, confidence interval; DHA, docosahexaenoic acids; EPA, eicosapentaenoic acids; N3, n-3 or omega-3 polyunsaturated fatty acids; N6, n-6 or omega-6 polyunsaturated fatty acids; Std, standard.

Figure 4

Forest plots showing effect sizes (Hedges’s g) and 95% confidence intervals (CIs) from individual studies and pooled results comparing n-3 PUFAs Levels, (a) DHA, (b) EPA, (c) n-3, (d) AA, (e) n-6, between ADHD population and control group. AA, arachidonic acids; ADHD, attention deficit hyperactivity disorder; CI, confidence interval; DHA, docosahexaenoic acids; EPA, eicosapentaenoic acids; N3, n-3 or omega-3 polyunsaturated fatty acids; N6, n-6 or omega-6 polyunsaturated fatty acids; Std, standard.