Essential element and toxic metal dyshomeostasis in childhood autism spectrum disorder: a comprehensive narrative review of correlations, tissue-specific distribution, and multifactorial regulation

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and repetitive stereotyped behaviors, with a rising global prevalence. Its etiology involves genetic, environmental, and epigenetic interactions, among which essential elements [including trace elements such as zinc (Zn), selenium (Se), copper (Cu), iron (Fe), manganese (Mn) and macrominerals like magnesium (Mg)] and toxic metals (lead (Pb), mercury (Hg), cadmium (Cd)) are key environmental regulators of neurodevelopment. This narrative review systematically summarizes the association between these elements and ASD in children. Core findings confirm that Zn/Se/Fe/Mg deficiency, tissue-specific Cu imbalance (elevated plasma, reduced hair), Pb/Hg accumulation, and Zn-Cu ratio imbalance are significantly correlated with ASD occurrence and severity. These abnormalities disrupt neurotransmitter homeostasis, oxidative stress balance, and synaptic plasticity, which pathways closely linked to ASD pathogenesis. Critically, we highlight the tissue-specific distribution patterns of these elements (differences across blood, hair, urine, and nails) and the multifactorial regulatory network involving genetic variants (e.g., metal transporter genes, metallothioneins), environmental exposures (diet, pollutants, pesticides), individual differences (age, gender), and comorbidities (gastrointestinal dysfunction). Intervention evidence shows that supplementing deficient essential elements or reducing toxic metal exposure may alleviate ASD symptoms, though study quality and methodological heterogeneity limit causal inferences. This review provides a theoretical basis for ASD pathogenesis research, early diagnosis, and targeted element-based interventions.