Effect of Treatment with OMEGA-3 Polyunsaturated Fatty Acids on Behavioural Measures in Children and Adolescents with Autism Spectrum Disorders

Background: Although there are some promising results, controversy regarding efficacy of polyunsaturated fatty acids (PUFAS) on clinical improvement of ASD remains (James et al, 2011). Recent developments suggest the existence of oxidative stress disturbances affecting lipid composition of neuronal membranes in ASD (James et al, 2006), mostly structural phospholipids rich on PUFAS. Most studies have also found low levels of PUFAS in autism (Chauhan et al, 2004). These alterations could potentially be reverted with oral PUFAS administration and yield, in turn, improvement on ASD clinical symptoms.

Objectives: To evaluate the effect of PUFAS ω-3 on behavioural measures in a sample of children and adolescents with ASD, and to test whether clinical effect correlates with biochemical outcomes.

Methods: Seventy-nine subjects with ASD were recruited from 3 centres in Spain. Inclusion criteria were: DSM-IV Pervasive Developmental Disorders (SCQ, clinical evaluation +/-ADOS); 5-17 years; and written informed consent. Exclusion criteria were: other Axis I DSM-IV Disorder; previous treatment with PUFAS or antipsychotics; modification of other psychopharmacologic treatments; liver disease; coagulation problems/anticoagulant treatment; pregnancy; breastfeeding. Study design: Crossover multicenter randomized double-blind clinical trial controlled with placebo. In phase I participants were randomized to receive 8-weeks of experimental treatment or placebo. Following a 2-week wash out phase, in phase II patients switched treatments for other 8-weeks period. Experimental treatment was fish oil with high concentration of PUFAS ω-3 (EPA + DHA) and vitamin E as stabilizer. Doses were adjusted by age:  5-11 years old  EPA 577.5 mg/day + DHA 385 mg/day+ vitamin E 1,6 mg/day;  12-17 years old EPA 693 mg /day + DHA 462 mg /day + vitamin E 2,01 mg/day (tid).  Placebo was liquid paraffin and vitamin E (same doses than in experimental treatment). Efficacy assessments were performed before and after phases I and II, and included behavioural (change in Social Responsiveness Scale (SRS) and Aberrant Behaviour Checklist (ABC-C)) and biochemical measures (level of PUFAS on erythrocyte membrane, total antioxidant oxidative stress in plasma, and plasma level of glutathione). Analyses were conducted in the per protocol sample: comparison of the change in any given outcome measure between phase on active treatment and on placebo (Student t-tests), intra-subject changes (repeated measures t-tests), and inter-subjects changes (mixed between-within analysis of variance, using age, baseline vitamin E and total dose of PUFAS ω-3 as covariates).

Results: 77 patients completed at least one visit (ITT) and 68 completed the whole protocol (PP). Both samples were comparable in terms of baseline characteristics. Mean age was 9.72 (SD 3.64) years. Treatment with PUFAS ω-3 did significantly improve SRS-total (p=0.046) and SRS-social motivation (p=0.001) scores from baseline to endpoint, with non-significant improvement on ABC-C scores. An increase in the ω-3 / ω-6 (p=0.003) in the erythrocyte membrane without changing plasma global antioxidant capacity was also found for PUFAS ω-3. There was no correlation between change in biological and behavioral measures.

Conclusions:  8 week treatment with a combination of EPA and DHA significantly improved SRS total and SRS-social motivation scores in children and adolescents with ASD. Correlation between biological and behavioral measures was not demonstrated.