Fish oil supplementation may improve attention, working memory, and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: A randomized crossover trial

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2x4 week crossover study, 26 participants were randomized to sequence of supplementation with fish oil (FO, 5.2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15%. Compliance was 94% and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0.3×SD (P=0.032) after FO vs SO, and the odds for d2 errors were 30% lower (P=0.016), which was supported by improved Conners scores of attention (P=0.023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3.5(-6.0;-1.0), n=10 vs -0.2(-2.5;2.2), n=11 without ADHD, P_interaction=0.096), who also improved their behavioural regulation index by 0.3×SD after FO (P_interaction=0.016). Participants without ADHD gained most in d2 test performance (OR=0.4(0.2;0.7) vs 0.9(0.6;1.3) in those with ADHD, P_interaction=0.002), but their executive function score was exacerbated after FO (5.9(0.0,11.8), P_interaction=0.039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.