Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials.

Omega-3 long chain polyunsaturated fatty acid supplementation (-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of -3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total -6 to total -3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of -3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using ² statistic. Fifteen case-control studies ( = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (-2.14 [95% CI -3.22 to -1.07]; < 0.0001; ² = 97%), EPA (-0.72 [95% CI -1.25 to -0.18]; = 0.008; ² = 88%), and ARA (-0.83 [95% CI, -1.48 to -0.17]; = 0.01; ² = 96%) and higher total -6 LCPUFA to -3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; = 0.02; ² = 74%). Four RCTs were included in meta-analysis 2 ( = 107). Compared with placebo, -3 LCPUFA improved social interaction (-1.96 [95% CI -3.5 to -0.34]; = 0.02; ² = 0) and repetitive and restricted interests and behaviours (-1.08 [95% CI -2.17 to -0.01]; = 0.05; ² = 0). Populations with ASD have lower -3 LCPUFA status and -3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of -3 LCPUFA.