A Placebo-Controlled Pilot Exploration of Cholesterol Supplementation for Autistic Symptoms in Children with Low Cholesterol

This pilot placebo-controlled trial (NCT00965068, 07/28/2009) explored effects of cholesterol supplementation on autism spectrum disorder (ASD) symptoms in children with abnormally low cholesterol. Fifteen children age 4–12 with ASD and cholesterol <5th percentile for age/sex were randomized to 225 mg cholesterol vs. matched placebo twice daily for 12 weeks, followed by 12-week open extension. The cholesterol daily dose approximated the amount in two eggs. Measures included the Ohio Autism Clinical Impression Scale (OACIS, primary outcome), and Peabody Picture Vocabulary Test (PPVT-4). Effect sizes were emphasized over statistical tests. On the OACIS-Improvement score for overall ASD symptoms, both groups improved, with cholesterol showing nominally (nonsignificantly) more improvement. The cholesterol group improved more than placebo by medium to large effects in OACIS-I nonverbal communication (d = −0.643); and OACIS-I problems with anxiety and fear (d = −0.671). Moreover, cholesterol showed significantly more improvement than placebo in PPVT-4 receptive language (p = 0.040). During the 12-week open extension, children originally assigned placebo improved significantly more in OACIS-I social interaction (p = 0.026, d = 1.170) from end of randomized phase than those receiving cholesterol throughout and improved more by large effects in OACIS-I aberrant behavior (d = 0.924), and anxiety/fear (d = 0.925). Graphs suggest continued open-trial improvement for the cholesterol group. Adverse events were similar between treatments. Cholesterol supplementation of children with ASD and cholesterol below the 5th percentile appears safe. The effect on communication, social interaction, and anxiety/fear looks encouraging; deserving further study, possibly over a longer period or at higher doses.