ArticlePloS one2016
Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers, Melatonin and Dopamine, for Brain Monoamine Neurotransmitters.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01617070 (Pilot Study to Evaluate Melatonin Secretion as a Marker of Decreased Serotonin in Individuals With PKU), which is not on this map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pilot Study to Evaluate Melatonin Secretion as a Marker of Decreased Serotonin in Individuals With PKU: Evaluation of the CNS Effects of Tetrahydrobiopterin
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria.Molecular genetics and metabolism · 2017Trial
- Review
- Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders.Cellular and molecular neurobiology · 2023Review
- Impact of Long-Rope Jumping on Monoamine and Attention in Young Adults.Brain sciences · 2021Article
- Large Neutral Amino Acids (LNAAs) Supplementation Improves Neuropsychological Performances in Adult Patients with Phenylketonuria.Nutrients · 2020Article
- Large neutral amino acid status in association with P:T ratio and diet in adult and pediatric patients with phenylketonuria.JIMD reports · 2019Article
- Article
- The molecular epidemiology of hyperphenylalaninemia in Uygur population: incidence from newborn screening and mutational spectra.Annals of translational medicine · 2019Article
- Salivary serotonin does not correlate with central serotonin turnover in adult phenylketonuria (PKU) patients.Molecular genetics and metabolism reports · 2018Article
- New protein structures provide an updated understanding of phenylketonuria.Molecular genetics and metabolism · 2017Review
- Altered tetrahydrobiopterin metabolism in patients with phenylalanine hydroxylase deficiency.European journal of pediatrics · 2017Article
- Multicompartment analysis of protein-restricted phenylketonuric mice reveals amino acid imbalances in brain.Journal of inherited metabolic disease · 2017Article
- Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria.PloS one · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPhenylketonuria (PKU) is due to a defective hepatic enzyme, phenylalanine (Phe) hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU.
objective(1) To evaluate the effects of sapropterin (BH4) and concurrent use of large neutral amino acids (LNAA) on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism. (2) To evaluate synergistic effects with BH4 and LNAA. (3) To determine the effects of blood Phe concentrations on the peripheral biomarkers concentrations.
methodsNine adults with PKU completed our study consisting of four 4-week phases: (1) LNAA supplementation, (2) Washout, (3) BH4 therapy, and (4) LNAA with BH4 therapy. An overnight protocol measured plasma amino acids, serum melatonin, and 6-sulfatoxymelatonin and dopamine in first void urine after each phase.
results(1) Three out of nine subjects responded to BH4. A significant increase of serum melatonin levels was observed in BH4 responders with decreased blood Phe concentration. No significant change in melatonin, dopamine or Phe levels was observed with BH4 in the subjects as a whole. (2) Synergistic effects with BH4 and LNAA were observed in serum melatonin in BH4 responders. (3) The relationship between serum melatonin and Phe showed a significant negative slope (p = 0.0005) with a trend toward differing slopes among individual subjects (p = 0.066). There was also a negative association overall between blood Phe and urine 6-sulfatoxymelatonin and dopamine (P = 0.040 and 0.047).
conclusionBlood Phe concentrations affected peripheral monoamine neurotransmitter biomarker concentrations differently in each individual with PKU. Melatonin levels increased with BH4 therapy only when blood Phe decreased. Monitoring peripheral neurotransmitter metabolites may assist in optimizing individualized treatment in PKU.
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Registered trials
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