Docosahexaenoic and Eicosapentaenoic Intervention Modifies Plasma and Erythrocyte Omega-3 Fatty Acid Profiles But Not the Clinical Course of Children With Autism Spectrum Disorder: A Randomized Control Trial

Abstract

BackgroundThe pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group.MethodsA double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group.ResultsThere were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention.ConclusionSpanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT03620097].

Alteration of Fatty Acid Profile in Fragile X Syndrome

“…Another open-label study of EPA and DHA supplementation (190 mg of EPA acid and 90 mg of DHA per 500 mg capsule; 2 capsules per day) on ten ASD children showed an improvement on the Autism Treatment Evaluation Checklist [40]. However, a recent double-blind, randomized placebo-controlled study on 54 ASD children showed that supplementation for 6 months with ω-3 FAs (including 800 mg/day of DHA and 25 mg/day of EPA) had no impact on clinical test scores [41].…”

“…Another double-blind placebo-controlled study of ω-3 FA supplementation with 600 mg EPA and 120 mg DHA for 16 months improved the working memory function in 55 ADHD children [43]. The studies on ASD and ADHD suggest that various ratios of EPA to DHA in ω-3 FA supplements have inconsistent effects on the clinical profile [41,43,44]. DHA and EPA are structural components of cell membranes in the central nervous system.…”

Dietary nutrients that potentially mitigate autism spectrum disorder and dietary recommendations for children and pregnant women

“…A randomized controlled trial indicated that omega‐3 fatty acids improve the fatty acid composition of erythrocyte membranes but do not alter the status of antioxidants in plasma and do not have significant therapeutic effects on ASD‐like phenotypes (Parellada et al., 2017). In addition, a double‐blind placebo‐controlled study found that a 6‐month intervention with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) did not improve clinical symptoms and did not have anti‐inflammatory effects in children with ASD (de la Torre‐Aguilar et al., 2022). In the future, large‐scale randomized controlled trials of various polyunsaturated fatty acids with potential ASD‐mitigating effects are needed to determine whether they have the desired effects and to provide research direction for molecular mechanism analyses in animal models.…”

Omega-3 polyunsaturated fatty acids and/or Vitamin D in Autism Spectrum Disorders ：A Systematic Review

“…EPA and DHA are found in natural foods and are mainly supplemented through diet or deep-sea fish oil [7]. DHA plays a role in cognitive function, neurotransmission, neuronal survival and attenuating neurodegeneration [8]. The balance of essential fatty acids is essential for brain development and considered as a possible biomarker for ASD [9].…”