Melatonin and energy metabolism in Autism Spectrum Disorder

Objectives: This study aimed at the characterization of patients with autism spectrum disorder in terms of their clinical, sleep, quality of life, metabolic and nocturnal urinary excretion profiles of six sulfatoxymelatonin, and to correlate these parameters with the urinary concentrations of this metabolite. It also evaluated the therapeutic response to the use of melatonin in terms of clinical, sleep, quality of life and metabolic profiles. Methods: This pilot project included 9 patients with autism spectrum disorder aged between 10 years and 16 years and 11 months, who were randomly assigned to placebo or melatonin groups (n= 4-5/group). Anamnesis, general physical examination, scales and questionnaires to assess autism spectrum disorder, sleep, quality of life, serum tests related to metabolism and analysis of the nocturnal urinary metabolite of melatonin were carried out. The actigraphy was used for 4 weeks pre-treatment and for the last 4 weeks of the treatment phase. Patients were classified as having or not metabolic syndrome and then randomized according to this classification. The intervention was double-blind, with 3 mg of immediate-acting melatonin, between 8 p.m. and 9 p.m., for 12 weeks. Guidance on melatonin and sleep was given before the intervention to all the patients. After eight weeks of treatment, the urinary metabolite of melatonin was measured in the night urine and in the second urine of the morning. Throughout the intervention, weekly telephone contact was made with the guardian. Results: There was a statistically significant improvement in the characteristics related to autism spectrum disorder and in the emotional aspects of quality of life in the melatonin group compared to pre-treatment. In the placebo group, compared to pre-treatment, there was a statistically significant improvement in various sleep parameters and emotional aspects of quality of life. Data from actigraphy showed a statistically significant change in which patients in the melatonin group went to bed and woke up earlier than at the start of the study. A reduction in systolic and diastolic blood pressure was observed, as well as a statistically significant worsening of the lipid profile in patients in the melatonin group compared to pre-treatment. The response of the glucose profile was variable and there was no statistically significant difference in the melatonin group. The melatonin metabolite in the second morning urine was elevated in all patients who used melatonin. Conclusions: Guidance on sleep and melatonin may have had a positive effect on sleep quality, aspects of autism spectrum disorder xxii and patients' quality of life. The use of melatonin in pediatrics may be beneficial not only for sleep parameters. Considering the important role of melatonin in metabolic physiology, studies are needed to establish the effect of melatonin treatment on energy metabolism parameters. The increased levels of 6-sulfatoxymelatonin in the second morning urine of all the patients in the melatonin group indicate excessive dosage and/or inappropriate timing. This could lead to excessive daytime sleepiness as well as harmful changes in metabolism. Studies are needed to establish the ideal dose for the use of melatonin in pediatrics.