Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia

Nutr Neurosci. 2010 Jun;13(3):135-43. doi: 10.1179/147683010X12611460763968.


A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Autistic Disorder / urine*
  • Child
  • Child, Preschool
  • Clostridioides difficile
  • Clostridium / metabolism
  • Clostridium Infections / complications
  • Clostridium Infections / drug therapy
  • Enterocolitis, Pseudomembranous / microbiology
  • Enterocolitis, Pseudomembranous / urine
  • Female
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Male
  • Middle Aged
  • Phenylalanine / metabolism
  • Phenylpropionates / urine*
  • Schizophrenia / complications
  • Schizophrenia / urine*
  • Sex Characteristics
  • Vancomycin / therapeutic use
  • Young Adult


  • Phenylpropionates
  • 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid
  • Phenylalanine
  • Vancomycin