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

Abstract

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.

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Correspondence to Nadja Rita Ging-Jehli.

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Nadja Ging-Jehli, Deepa Manda, Elizabeth Hurt, and Stacey Moone have no conflicts of interest to disclose. Dr. Arnold has received research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, Shire, Supernus, Roche, and YoungLiving (as well as NIH and Autism Speaks), has consulted with Gowlings, Neuropharm, Organon, Pfizer, Sigma Tau, Shire, Tris Pharma, and Waypoint, and been on advisory boards for Arbor, Ironshore, Novartis, Noven, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire. Dr. Hollway has received research contracts, or research support from Forest Research Institute, Sunovion Pharmaceuticals, F. Hoffman-La Roche, Supernus, Young Living, Autism Speaks, and the NIH. She has served on the advisory board for YAMO Pharmaceuticals and has consulted with MedAvante-ProPhase.

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Ging-Jehli, N.R., Manda, D., Hollway, J. et al. A Placebo-Controlled Pilot Exploration of Cholesterol Supplementation for Autistic Symptoms in Children with Low Cholesterol. J Dev Phys Disabil 33, 819–837 (2021). https://doi.org/10.1007/s10882-020-09776-4

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Keywords

  • Cholesterol supplementation
  • Autism
  • Low cholesterol
  • Smith-Lemli-Optiz syndrome
  • Complementary/alternative treatment