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

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.

Dietary Phosphate and the Forgotten Kidney Patient: A Critical Need for FDA Regulatory Action.

Careful dietary management that reduces high phosphate intake is recommended to slow the progression of chronic kidney disease (CKD) and prevent complications of CKD and may help reduce chronic disease risks such as incident CKD associated with high phosphate intake in the healthy general population. For patients treated with maintenance dialysis, control of serum phosphorus levels is considered a marker of good care and requires a coordinated plan that limits dietary phosphate intake, uses oral phosphate binders, and provides an adequate dialysis prescription. Even with traditional thrice-weekly hemodialysis or peritoneal dialysis, use of phosphate binders, and a concerted effort to limit dietary phosphate intake, adequately controlled serum phosphorus levels are not possible in all dialysis patients. Efforts to limit phosphate intake are thwarted by the underestimated and unquantified phosphate content of processed foods and some medications due to the hidden presence of phosphate additives or excipients added during processing or drug formulation. Effectively limiting phosphate intake could potentially be achieved through simple US Food and Drug Administration regulatory actions. Mandatory labeling of phosphate content on all packaged foods and drugs would enable identification of healthy low-phosphate foods and medications and permit critically important control of total phosphate intake. Simple changes in regulatory policy and labeling are warranted and would enable better management of dietary intake of phosphate at all stages of kidney disease, as well as potentially reduced health risks in the general population.