Effects of Supplementation With Antioxidant Agents on Sleep in Autism Spectrum Disorder: A Review

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition, whose etiology remains poorly understood in most cases. Several genetic, epigenetic and environmental factors have been implicated in ASD pathogenesis and numerous studies have provided evidences for increased levels of oxidative stress and reduced antioxidant capacity in patients with ASD. Recent clinical trials explored supplementation with antioxidant agents as a potential therapeutic strategy for ASD, investigating the impact of this treatment on behavioral symptoms and on most common comorbidities of the disease, including sleep disturbances. Among all medical conditions associated to ASD, sleep problems are highly prevalent and are supposed to be positively related to the severity of the disease. Moreover, studies on animal models support the hypothesis of a relationship between oxidative stress and sleep deprivation. The aim of this review is to summarize the current state of the literature on the effect of antioxidant treatment on sleep disturbances in patients with ASD. Twenty-one articles were included in final synthesis. Of them, 15 studies involved Melatonin, 1 Tryptophan and 5 focused on supplementation with other antioxidant agents (namely Coenzyme Q10, L-Carnosine, Luteolin and Quercetin). Despite the high prevalence of comorbid sleep troubles in ASD, there is a paucity of data on the efficacy of antioxidant agents in those patients. Further research is needed to better define the role of antioxidants agents as adjunctive therapy in the management sleep disorders in children and adolescents affected with ASD.

Chronic Administration of Melatonin: Physiological and Clinical Considerations

“…Multiple studies of melatonin (e.g., both immediate-release and extended-release) in ASD have shown that melatonin decreases the time to sleep onset, increases sleep duration, and decreases nighttime awakenings. The nighttime administration of melatonin was also shown to improve daytime behaviors in children with ASD [ 14 , 15 , 16 ]. However, some research has shown that melatonin use in children may affect hormonal development, mainly delaying the onset of puberty [ 17 ].…”

Autism Spectrum as an Etiologic Systemic Disorder: A Protocol for an Umbrella Review

“…These changes in the mechanisms of absorption, or the permeability of the intestinal epithelial mucosa, can lead to an inflow of toxic or foreign organic or inorganic substances causing changes in immunological or metabolic defenses. That can ultimately affect the nerve pathways at the level of the large gastrointestinal nervous complex, or extend directly or indirectly to the central nervous system [ 24 , 25 ].…”

“…People with ASD are exposed to the negative effects of chemical and environmental risks, such as aluminium from food packaging and cadmium from air pollution [ 7 ]. Since several studies report that ASD people struggle to eliminate toxins from the body, there may be an increased probability of a positive effect from taking antioxidant supplements [ 24 , 25 ].…”

Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels

“…6–14 It has been postulated that misalignment of melatonin rhythm is involved in the etiology of these sleep problems, a crucial component of circadian rhythm regulation, including sleep-wake cycles. 1,15–20…”

“…3 Of the drugs used in therapy, melatonin deserves special consideration, not only because it is one of the most commonly used pharmacologic treatments but also because it is frequently sold as a nutritional supplement although it has been relatively underexamined. 16,17,22,23…”