“Nutritional Supplementation in Children with Autism Spectrum Disorders (ASD) in Qatar: Effects on the Methionine-Transsulfuration Cycle and Behavior”

Background:

  Several factors are suggested to contribute to ASD. Earlier studies have demonstrated defective synthesis of neurotransmitters and both pharmacological and non-pharmacological measures have been used to enhance neurotransmission. An example of the latter approach is nutritional supplementation. Very few studies have systematically analyzed the effects of vitamins and minerals on both biochemical parameters, (e.g. related to the synthesis of neurotransmitters involving the methionine cycle), and behavior.

Objectives:

To investigate the effects of a widely used nutritional supplement containing vitamin B₆ and Mg²⁺ on the methylation-transsulfuration pattern of the MC and on behavior in children with ASD (according to the criteria of DSM-IV R) in an out-patient setting in Qatar.

Methods:  

31 patients (4 females, 27 males), 3- 9 years of age, were randomized into two parallel groups to receive either a placebo formulation (16 patients; control group) or a commercial, nutritional supplementation containing vitamin B₆ and Mg²⁺ (15 patients; treatment group) for 12 weeks. The patients’ behavior was evaluated with the Child Autism Rating Scale (CARS) and the Autism Treatment Evaluation Checklist (ATEC). Blood samples were collected and analyzed (University of Heidelberg, Germany) for the contents of amino acids (AA) and intermediates of the methionine cycle (methionine, homocysteine, cystothionine, cysteine and glutathione) prior to and after treatment. The patients in both groups continued to participate in the regular educational program at the clinic during the trial.

Statistical Methods: Chi-square test was used to examine the association between various qualitative measurements and outcome mean of quantitative variables were compared using paired and unpaired t tests. All analyses were performed with the statistical packages SPSS 18.0.

Results:  

Subjects in the treatment group demonstrated significantly decreased levels of homocysteine (means: 3.66 ± 2.74 post- vs. 5.71 ± 2.67 pre treatment; p= 0.006).

Between treatment comparision revealed that Homocysteine levels were significantly reduced in the treatment group than placebo ( p= 0.034).

Although not statistically significant, the levels of methionine and cysteine were also reduced in patients receiving treatment compared to the control group. There were no differences in the levels of measured amino acids prior to or after treatment.

The patients in the treatment group showed improved scores in the CARS test (post- vs. pre-treatment, p<0.0001).

 Although, not statistically significant, the results of the ATEC test demonstrated also a trend towards improvement in the treatment group.

No significant adverse reactions were observed or reported for the two groups.

Conclusions:  

This randomized, placebo-controlled, double blind pilot trial demonstrates that a multivitamin preparation containing vitamin B₆ and Mg²⁺ can enhance both behavior and metabolic parameters associated with a defective methionine cycle in children with ASD. Furthermore, the use of this preparation was found to be safe and without significant side effects.