Tetrahydrobiopterin in the Treatment of Children With Autistic Disorder

Abstract

Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.

Medical Therapies for Children With Autism Spectrum Disorder—An Update

“…104,105 Children in the GFCF diet also improved significantly on tests of cognitive skills, motor skills, verbal and social communication, anxiety, and reaction to changes in environment and routine compared with control children (p values <0.05). Another high risk of bias RCT with 24-month followup of participants reported few differences in behavioral measures between children on a GFCF diet and those with no dietary restrictions; 64,65 scores on the Autism Diagnostic Observation Schedule (ADOS) and Gilliam Autism Rating Scale improved significantly in participants in the GFCF group vs. no diet group at 12 months, but scores were not different on any measure in a subset of participants followed for 24 months.…”

“…We considered 39 studies to have low risk of bias, 56,61,62,64,65,88,104,105,120,123 Despite the high number of low and moderate risk of bias studies, few studies addressed the same interventions or outcomes, and most studies included few participants, evaluated only in the short term (<6 months); thus, evidence for many agents remains insufficient. Table 5 outlines key study characteristics.…”

“…Four RCTs (in multiple publications) compared GFCF diets to either an unaltered diet, 64,65,[104][105][106][107] or a low sugar diet (Total N across studies=82). 63 One 12-week RCT (moderate risk of bias) reported no significant differences between groups on measures of development or behavior (Mullen Scales of Early Learning, Child Behavior Checklist), though the control group improved significantly from baseline on visual reception, withdrawal, aggression, and attention subscales (p values <0.05) Another 12-week crossover RCT (moderate risk of bias) similarly reported no significant differences between groups on measures of symptom severity or language, though parents of 7 of the 15 children participating in the study reported improvements in language.…”

“…Studies addressed nutritional supplements including omega-3 long-chain free fatty acid (FFA) supplementation, [80][81][82]84 methyl-B12 supplement, 83,87 digestive enzymes, 85,117 and L-carnitine. 86,88 Dietary interventions addressed in studies included GFCF diets, 58,[62][63][64][65][104][105][106][107] gluten/casein challenge foods, 59,60 and camels' milk. 61 Studies were conducted in the United States, 58, 60, 63, 80-83, 87, 88, 106, 107, 128 Australia, 117 Belgium, 59 Denmark, 64,65 Egypt, 85,86 Iran, 62 Holland, 84 Norway, 104,105 and Saudi Arabia.…”

“…86,88 Dietary interventions addressed in studies included GFCF diets, 58,[62][63][64][65][104][105][106][107] gluten/casein challenge foods, 59,60 and camels' milk. 61 Studies were conducted in the United States, 58, 60, 63, 80-83, 87, 88, 106, 107, 128 Australia, 117 Belgium, 59 Denmark, 64,65 Egypt, 85,86 Iran, 62 Holland, 84 Norway, 104,105 and Saudi Arabia. 61 Study treatment durations ranged from 7 days to 2 years, and sample sizes ranged from 12 to 92 (total N=732).…”