Dysregulated phosphate metabolism in autism spectrum disorder: associations and insights for future research

Abstract

Studies of autism spectrum disorder (ASD) related to exposure to toxic levels of dietary phosphate are lacking. Phosphate toxicity from dysregulated phosphate metabolism can negatively impact almost every major organ system of the body, including the central nervous system. The present paper used a grounded theory-literature review method to synthesise associations of dysregulated phosphate metabolism with the aetiology of ASD. Cell signalling in autism has been linked to an altered balance between phosphoinositide kinases, which phosphorylate proteins, and the counteracting effect of phosphatases in neuronal membranes. Glial cell overgrowth in the developing ASD brain can lead to disturbances in neuro-circuitry, neuroinflammation and immune responses which are potentially related to excessive inorganic phosphate. The rise in ASD prevalence has been suggested to originate in changes to the gut microbiome from increasing consumption of additives in processed food, including phosphate additives. Ketogenic diets and dietary patterns that eliminate casein also reduce phosphate intake, which may account for many of the suggested benefits of these diets in children with ASD. Dysregulated phosphate metabolism is causatively linked to comorbid conditions associated with ASD such as cancer, tuberous sclerosis, mitochondrial dysfunction, diabetes, epilepsy, obesity, chronic kidney disease, tauopathy, cardiovascular disease and bone mineral disorders. Associations and proposals presented in this paper offer novel insights and directions for future research linking the aetiology of ASD with dysregulated phosphate metabolism and phosphate toxicity from excessive dietary phosphorus intake.

Copy number variations in autistic children

“…Genetic and functional studies show that these enzymes are often dysregulated in ASD ( 93-96 ). Understanding the dysregulation of phosphoinositides may offer opportunities to manage ASD in an improved way ( 96 ).…”

A Mendelian randomization study of the effect of mental disorders on cardiovascular disease

“…These pieces of evidence support ASD as a potential risk factor for CVD, which is consistent with our findings. Interestingly, a recent study has found that the mechanism of comorbidity between ASD and CVD may be related to dysregulated phosphate metabolism ( 60 ), which provides a new direction for future research.…”