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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

Mazahery H, Stonehouse W, Delshad M, Kruger MC, Conlon CA, Beck KL, von Hurst PR (2017) Nutrients 19;9(2) 155. doi: 10.3390/nu9020155. 

Web URL: View this and related research articles via PubMed here. Free full text of this article is available


Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-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 n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-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 I² statistic.

Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (-2.14 [95% CI -3.22 to -1.07]; p < 0.0001; I² = 97%), EPA (-0.72 [95% CI -1.25 to -0.18]; p = 0.008; I² = 88%), and ARA (-0.83 [95% CI, -1.48 to -0.17]; p = 0.01; I² = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I² = 74%).

Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (-1.96 [95% CI -3.5 to -0.34]; p = 0.02; I² = 0) and repetitive and restricted interests and behaviours (-1.08 [95% CI -2.17 to -0.01]; p = 0.05; I² = 0).

Populations with ASD have lower n-3 LCPUFA status and n-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 n-3 LCPUFA.


In ASD children, this systematic review generated two meta-analyses - one pooling results from 15 case-control studies investigating blood concentrations of omega-3, and the other combining 4 clinical trials of omega-3 supplementation for ASD symptoms.

The main results were:

1) ASD children show lower blood concentrations of the long-chain omega-3 DHA, and the long-chain omega-6 AA, than controls

2) Controlled trials show preliminary evidence that omega-3 supplementation may help to reduce some core ASD symptoms - repetitive and restricted interests and behaviours, and social interaction - as well as hyperactive behaviour problems.

More research is needed to confirm and extend these findings, which help to confirm and extend those from previous studies.  See for example:

And for more information on this topic, please see the following lists of news and research articles, which are regularly updated: