title: Melatonin and dopamine as biomarkers to optimize treatment in phenylketonuria: effects of tryptophan and tyrosine supplementation.
abstract: OBJECTIVE
  To determine whether additional supplementation of tryptophan (Trp) and tyrosine (Tyr) improve serotonin and dopamine metabolism in individuals with phenylketonuria treated with large neutral amino acid (LNAA) tablets.
  
  
  METHODS
  Ten adult individuals with phenylketonuria participated in a randomized, double-blind, placebo-controlled cross-over study consisting of three 3-week phases: washout, treatment with LNAA tablets plus supplementation with either Trp and Tyr tablets or placebo, and LNAA tablets plus the alternate supplementation. An overnight protocol to measure blood melatonin, a serotonin metabolite in the pinealocytes, and urine 6-sulfatoxymelatonin and dopamine in first-void urine specimens was conducted after each phase.
  
  
  RESULTS
  Serum melatonin and urine 6-sulfatoxymelatonin and dopamine levels were increased in the LNAA phase (LNAA plus placebo) compared with the washout phase. Serum melatonin and urine 6-sulfatoxymelatonin were not increased in the active phase (LNAA plus Trp + Tyr) compared with the LNAA phase, although plasma Trp:LNAA was increased compared with the LNAA phase. Among 7 subjects with a plasma Trp/LNAA >0.03, a negative correlation between urine 6-sulfatoxymelatonin and plasma phenylalanine levels was observed (r = -0.072). Urine dopamine levels and plasma Tyr:LNAA were increased in the active phase compared with the LNAA phase.
  
  
  CONCLUSIONS
  Melatonin levels were not increased with the higher dose of Trp supplementation, but dopamine levels were increased with the higher dose of Tyr supplementation. Serotonin synthesis appears to be suppressed by high phenylalanine levels at the Trp hydroxylase level.
authors.affiliation: Genetics Division, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yano
authors.affiliation: Genetics Division, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Moseley
authors.affiliation: Clinical and Translational Science Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Azen
mesh_terms: D000328:Adult; D021542:Amino Acids, Neutral / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004298:Dopamine / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000097:blood* / Q000652:urine; D008875:Middle Aged; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D012701:Serotonin / Q000378:metabolism; D016896:Treatment Outcome; D014364:Tryptophan / Q000627:therapeutic use*; D014443:Tyrosine / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D021542:Amino Acids, Neutral; D015415:Biomarkers; C054513:6-sulfatoxymelatonin; D012701:Serotonin; D014443:Tyrosine; D014364:Tryptophan; D008550:Melatonin; D004298:Dopamine