Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?

Med Hypotheses. 2013 Jan;80(1):1-12. doi: 10.1016/j.mehy.2012.08.035. Epub 2012 Oct 23.


First reported formally in 1980, the frequent ability of infectious fever to relieve autistic behavior, often dramatically (and rarely aggravate), has long tantalized parents, practitioners, and researchers - yet its physiology and biochemistry have never been investigated, to judge from the literature. Fever is a complex interplay of immune, metabolic, and stress responses, yet its benefit in autistic disorders (ASD) may derive largely from a single response - release of the amino acid glutamine from skeletal muscles as provisional fuel. This proposal is based on evidence of low blood and brain glutamine in ASD children and adults, notable lack of autistic behavior in children with high brain glutamine from urea cycle disorders, and other events that elicit dramatic improvements - fasting, panic, pain, and the corticosteroid prednisone - that release or synthesize glutamine. Glutamine released from muscles is metabolized by the intestines like ingested glutamine. If glutamine released by fever rarely aggravates autistic behavior, why would supplemental glutamine?

MeSH terms

  • Ammonia / metabolism*
  • Autistic Disorder / complications
  • Autistic Disorder / metabolism
  • Autistic Disorder / physiopathology*
  • Brain / metabolism*
  • Energy Metabolism / physiology
  • Fasting / metabolism
  • Fever / complications
  • Fever / metabolism
  • Fever / physiopathology*
  • Glutamine / metabolism*
  • Humans
  • Muscle, Skeletal / metabolism*
  • Panic / physiology
  • Prednisone / pharmacology
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • Glutamine
  • Ammonia
  • Sodium-Potassium-Exchanging ATPase
  • Prednisone