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

Abstract

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.

Understanding environmental contributions to autism: Causal concepts and the state of science

“…Polyunsaturated fatty acids (PUFAs), especially omega-3, play significant roles in the structure, function, and development of human brains [Freeman et al, 2006;McNamara & Carlson, 2006;Rombaldi Bernardi, de Souza Escobar, Ferreira, & Pelufo Silveira, 2012]. Differential PUFA status in individuals with versus without ASD [Brigandi et al, 2015;Jory, 2016;Wiest, German, Harvey, Watkins, & Hertz-Picciotto, 2009;Yui, Imataka, Kawasaki, & Yamada, 2016], and small studies of fatty acid supplementation to improve ASD symptoms were recently reviewed [Mazahery et al, 2017]. Omega-3 consumption during pregnancy has been associated with higher IQ [Richardson, Easton, & Puri, 2000b] and fewer social problems [Richardson & Ross, 2000].…”

Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy

“…Omega-3 Omega-3 fatty acids have anti-inflammatory and immunomodulatory properties [151][152][153]. Supplementation with omega-3 decreases NF-κB, IL-12, and IL-13 gene expression [154], and levels of macrophage inflammatory protein (MIP)-2, IL-6 [155], IL-17A [156], and TNF-α [155][156][157][158].…”

“…Supplementation with omega-3 decreases NF-κB, IL-12, and IL-13 gene expression [154], and levels of macrophage inflammatory protein (MIP)-2, IL-6 [155], IL-17A [156], and TNF-α [155][156][157][158]. Despite being widely used as an alternative practice in children with ASD [159,160], omega-3 supplementation cannot be recommended based on the evidence that is currently available [151,[160][161][162][163][164].…”

Inflammation (IL-1β) Modifies the Effect of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids on Core Symptoms of Autism Spectrum Disorder—An Exploratory Pilot Study

“…It is generally agreed that ASD is driven by an interaction between genetic and non-genetic factors (such as nutritional factors) [25]. There is some data to support a role for vitamin D and omega-3 long chain polyunsaturated fatty acids (LCPUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the development and management of ASD, though the findings are mixed [26,27]. These nutrients have immunomodulatory, anti-inflammatory and anti-oxidant properties, and both have important roles in brain function and structure and in the neurotransmitter system [26][27][28].…”

“…The efficacy of vitamin D and omega-3 LCPUFA in improving ASD-related symptoms has been tested in a few randomised controlled trials. However, the results from these trials are mixed and inconclusive [26,27]. Using the Social Responsiveness Scale (SRS) (total and domains) questionnaire, our research group previously investigated the effect of vitamin D, omega-3 LCPUFA or both on core symptoms of ASD (VIDOMA trial) and also found mixed results [43].…”