Double Masked Placebo Controlled Trial of Cholesterol in Hypocholesterolemic ASD

We have performed pilot work suggesting that some individuals with autism spectrum disorders (ASD) have very low blood cholesterol levels. This low cholesterol and other conditions with low sterols (cholesterol is in the family of sterols) may be an important marker for subtypes of ASD. The proposed trial aims to test the response of individuals with ASD and low cholesterol to increased cholesterol in the diet.  

In this study, three sites will collaborate to determine the rate of very low cholesterol (hypocholesterolemia) in ASD. In addition, 60 youths (20 at each site) with ASD and low cholesterol will receive extra cholesterol or a placebo (fake medicine) over 12 weeks in a study in which neither the parent nor the doctor knows which one the youth is taking. The response will be measured by standard tests of behavior, communication and other autism features.  

Evidence for the role of low cholesterol in causing ASD in a subgroup of individuals comes from five sources: first, half of the individuals with Smith-Lemli-Opitz syndrome (SLOS) meet the behavioral criteria for autistic disorder (Tierney et al, 2001) and three quarters have some type of ASD (Sikora et al, 2006). Second, we found that in individuals with SLOS, the lower the cholesterol was in the blood and cerebrospinal fluid, the more severe were the autism, IQ, and adaptive function deficits. Third, in SLOS, we found improvement in social and communication abilities with added dietary cholesterol. Fourth, cholesterol was low in a pilot study of 200 children with autism of unknown cause (Tierney et al, 2006). Fifth, it is becoming increasingly clear that cholesterol plays a pivotal role in several aspects of brain development.  

This proposal is designed to 1) determine how often abnormally low cholesterol occurs and what the individuals with ASD with low cholesterol are like in behavior, appearance, intelligence, and language, and 2) treat individuals with ASD who have very low cholesterol blood levels to see if these features improve.  

What this means for people with autism: These findings will guide the medical community in identifying individuals who should be tested for sterol disorders. This study will also help us learn whether adding extra cholesterol to the diet will improve behavioral and other autism spectrum characteristics seen in individuals with ASD and low cholesterol.