Zinc and Copper Metabolism and Risk of Autism: a reply to Sayehmiri et al

Abstract Objective Sayehmiri et al. recently conducted a meta-analysis to explore the relationship between zinc and copper metabolism and autism spectrum disorders (ASD). Recent reports have elucidated a full behavioral profile of mice exposed to prenatal zinc deficiency and documented a phenotype similar to that found in autism spectrum disorders (ASD). These studies suggest that significant alterations in Zn metabolism may be an important nutritional component in the development of ASD. Materials & Methods The idea that prenatal zinc deficiency may be to blame is cursorily challenged. Epidemiological studies show that high-income countries with a low estimated prevalence of inadequate zinc intake report the highest prevalence of ASD. Consistent with other reports indicating a link between air pollution and ASD, it has recently been proposed that use of the herbicide, glyphosate, in agriculture may serve as an instrumental variable in predicting later neurodevelopmental impairment via emissions of the agricultural air pollutant, nitrous oxide (N2O). Results Work in anesthesiology has demonstrated the neurological effects from subanesthetic doses of N2O, including its inhibition of the alpha 7 nicotinic acetylcholine receptor (?7), a receptor coupled to both central nitric oxide (NO) metabolism and peripheral anti-inflammation. Conclusion This correspondence explores how the aforementioned nutritional phenotypes found by Sayehmiri et al. in their systematic review may be a compensatory mechanism to counter the effects (namely, ?7 inhibition) of air pollutant exposures occurring during the most critical stages of fetal development.