Therapeutic effects of larger doses of arachidonic acid added to DHA on social impairment and its relation to alterations of polyunsaturated fatty acids in individuals with autism spectrum disorders

The polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and docosahexaenoic acid (DHA) may play key roles in brain network maturation. ARA plays an important role in signal transduction related to neuronal maturation. This study aims to evaluate the efficacy of supplementing with larger doses of ARA added to DHA in a double-blind, placebo-controlled 16-week trial. To confirm findings observed in the placebo-controlled trial, an additional 16-week open-label study was further conducted. To examine the relationship between the efficacy of the supplementation regimen and alterations in PUFAs levels, we examined plasma levels of PUFAs. We used the Social Responsiveness Scale (SRS) and the Aberrant Behavior Checklist-Community (ABC) to estimate psychotic symptoms. Repeated measures ANOVA revealed that this supplementation significantly improved SRS-measured communication as well as ABC-measured social withdrawal during the placebo-controlled trial. The treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: 0.87 vs. 0.44; social withdrawal: 0.88 vs. 0.54). At the end of the placebo-controlled trial, there was a significant difference in the change in plasma ARA levels from the baseline and a trend towards a significant difference in plasma ARA levels between the two groups. The open-label study was not powered to detect significant improvements in the outcome measures or significant differences in plasma ARA levels. The present clinical trials suggest that supplementation with larger ARA doses added to DHA improves social impairment in individuals with ASD via ARA-induced upregulation of neuronal functioning.