Effects of Carnosine Supplementation on Plasma Levels of Advanced Glycation and Precursors of Lipoxidation End Products Markers in Children with Autism Spectrum Disorders

Abstract

Background and objective: Autism is a disorder with impaired communication and interactions, repetitive patterns of behaviors and limited interests. Increased oxidative stress has been reported in autistic patients. Besides, evidence linking oxidative stress to enhancement of advanced glycation and lipoxidation end products (AGEs and ALEs) and their precursors. Carnosine is a natural dipeptide with anti-glycation effects. Therefore, with the assumption of the effect of carnosine on the modification of the AGEs, ALEs and their precursors, we aimed to investigate the beneficial effects of carnosine on reducing AGEs and precursors of ALEs in children with autism. Method: In this randomized double blind placebo controlled clinical trial study, 54 children, 36 autistic and 18 healthy, participated. Children with autism were divided to two groups of carnosine (N=18) and placebo (N=18). The carnosine group received 500 mg/day of carnosine capsule and the placebo group received 500 mg/day of starch capsule, for 8 weeks. Plasma levels of AGEs include methylglyoxal (MG), carboxy methyllysine (CML) and pentosidine (Pen) and precursors of ALEs include malondialdehyde (MDA) and 4-hydroxy nonenal (4-HNE) were measured and compared before intervention in these 54 children. Then, supplement of 500 mg/day carnosine or placebo was performed for two months in autistic subjects. Plasma levels of AGEs and precursors of ALEs were measured by ELISA method. Severity of autism, gastrointestinal disorders, sleep disturbances and hyperactivity were measured by GARSII questionnaire, QPGS-ROMEIII questionnaire, CSHQ questionnaire, and parent Conners questionnaire, respectively. Results: Most of the children with autism (63.9%) were in normal range of body mass index. Also, the majority of these children suffered from gastrointestinal problems (69.4%), sleep disturbances (94.4%) and hyperactivity (66.7%). Plasma levels of AGEs (MG, CML and Pen) and precursors of ALEs (MDA and 4-HNE) in autistic children was comparable with healthy children (P>0.05). Carnosine supplementation did not significantly alter plasma levels of AGEs (MG, CML and Pen) and precursors of ALEs (MDA and 4-HNE) in children with autism. There was a positive significant correlation between cyclic vomiting syndrome and malondialdehyde (r = 0.334, p=0.047) and adolescence rumination and methylglyoxal (r = 0.344, p = 0.40) but there was no correlation between the factors studied and sleep disorders, hyperactivity and severity of autism (p>0.05). Conclusion: In the present study, there was no significant difference in plasma levels of AGEs and precursors of ALEs between autistic and healthy subjects. Additionally, carnosine supplementation did not differ in plasma levels of AGEs and precursors of ALEs in children with autism. There was a significant correlation between plasma levels of AGEs and ALE precursors together and some gastrointestinal disorders.