Melatonin and dopamine as biomarkers to optimize treatment in phenylketonuria: effects of tryptophan and tyrosine supplementation.

[phenylketonuria]

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 .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 .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 .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 .