Therapies for Children With Autism Spectrum Disorders

Dietary and Other Medical Interventions
Additional studies in the medical literature addressed the use of dietary interventions
(including special diets) as well as medical therapies for sleep and gastrointestinal dysfunction,
hyperbaric oxygen, and other agents.
Content of the literature-dietary interventions. We identified eight studies conducted in the
clinic setting that addressed the use of various oral dietary supplements to treat ASDs in children,
including ages ranging from one to 18 years; interventions included iron, 242 magnesium-vitamin
B6, 243 melatonin, 244 ketogenic diet, 245 and fish oil and evening primrose oil. 246 Two studies
focused on amino acid derivatives, including L-carnosine 247 and N,N dimethylglycine, 248 and one
on a digestive enzyme supplement. 249
Studies measured a wide range of outcomes, with little overlap in instruments utilized among
the studies. Most studies analyzed outcomes after 18 days to 3 months; 242,246-249 one study
assessed outcomes after 6 months, 245 one study after a mean of eight months, 243 and one
examined data at a mean of 1.8 years of followup. 244 Five studies reported adverse
events. 242,245,248-250 Table 17 includes additional study information.
Summary of the literature-dietary interventions. Two RCTs explored dietary supplementation
with amino acid derivatives in ASDs. The 8-week RCT of daily L-carnosine supplementation
was conducted at a specialty clinic and included 31 children ages three to twelve years with
ASDs. 247 Significant changes on the CGI at 2 weeks compared with 6 weeks were observed in
the L-carnosine group; significant effects on receptive vocabulary and GARS scores were also
observed before vs. after treatment in this group. However, no significant changes were observed
between groups in the Gilliam Autism Rating Scale measure of ASDs severity, Receptive and
Expressive Picture Vocabulary scores, or parent-rated CGI measure of overall improvement.
Adverse effects in the L-carnosine group included sporadic hyperactivity and were alleviated by
dose reduction.
The 4-week randomized controlled trial of daily N,N-dimethylglycine treatment was
conducted at an academic clinic and included 37 children with ASDs ages three to eleven
years. 248 The dimethylglycine group did not improve more than the placebo group on any
behavioral measure (VABS, ABC-C). There was no significant effect on neurologic examination
of motor skills, muscle tone, or coordination. Adverse effects in the dimethylglycine group were
similar to placebo.
A six month, double blind, crossover RCT of a digestive enzyme supplement (Peptizyde)
which combines the enzymes peptidase, protease 4.5, and papain, included 43 children between
the ages of 3 and 8 years (mean= 69.4 months). 249 Most participants (84 percent) were diagnosed
with autistic disorder. Participants were randomized to either enzyme for three months followed,
after a one-week washout period, by placebo (n=21) or placebo for three months (one-week
washout period) followed by enzyme (n=22). Sixteen participants (10 in the enzyme/placebo
group and 6 in placebo/enzyme) dropped out of the study for reasons including a parentperceived
increase in negative behavior and child refusal to eat food with contents of enzyme
capsules added. In intention to treat analyses, investigators reported significant differences
between enzyme and placebo only on a measure of food selectivity, which was not sustained
over the study period. Investigators noted no serious adverse effects though four children
withdrew from the study because of behavioral deterioration perceived by parents. The authors
also assessed potential effects of alternative therapies, multivitamins, prescription medications,
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