Trial reportThe Journal of pediatrics2013
Large neutral amino acid supplementation increases melatonin synthesis in phenylketonuria: a new biomarker.
Trial report in The Journal of pediatrics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Tyrosine supplementation for phenylketonuria.The Cochrane database of systematic reviews · 2021Pooled it
- Single amino acid supplementation in aminoacidopathies: a systematic review.Orphanet journal of rare diseases · 2014Pooled it
- 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
- Melatonin and dopamine as biomarkers to optimize treatment in phenylketonuria: effects of tryptophan and tyrosine supplementation.The Journal of pediatrics · 2014Trial
- Genetic etiology and clinical challenges of phenylketonuria.Human genomics · 2022Review
- Potential Therapeutic Effects of Melatonin Mediate via miRNAs in Cancer.Biochemical genetics · 2022Review
- Large neutral amino acid status in association with P:T ratio and diet in adult and pediatric patients with phenylketonuria.JIMD reports · 2019Article
- Large Neutral Amino Acid Therapy Increases Tyrosine Levels in Adult Patients with Phenylketonuria: A Long-Term Study.Nutrients · 2019Article
- Article
- Salivary serotonin does not correlate with central serotonin turnover in adult phenylketonuria (PKU) patients.Molecular genetics and metabolism reports · 2018Article
- Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels.Journal of nutrition and metabolism · 2018Article
- Urinary sulphatoxymelatonin as a biomarker of serotonin status in biogenic amine-deficient patients.Scientific reports · 2017Article
- Article
- Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations.Aging and disease · 2015Review
- Article
- Differential effects of low-phenylalanine protein sources on brain neurotransmitters and behavior in C57Bl/6-Pah(enu2) mice.Molecular genetics and metabolism · 2014Article
- Recommendations for the nutrition management of phenylalanine hydroxylase deficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2014Review
- Advances in the nutritional and pharmacological management of phenylketonuria.Current opinion in clinical nutrition and metabolic care · 2014Review
- Is melatonin synthesis a new biomarker for the pathogenesis and treatment of phenylketonuria?The Journal of pediatrics · 2013Article
- Phenylketonuria: A new look at an old topic, advances in laboratory diagnosis, and therapeutic strategies.International journal of health sciencesReview
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTo determine whether levels of melatonin in blood and urine can serve as a peripheral biomarker to reflect brain serotonin synthesis in individuals with phenylketonuria (PKU). STUDY
designWe measured the levels of melatonin, a serotonin metabolite in the pinealocytes, in the blood and urine of individuals with PKU in a randomized double-blind placebo controlled crossover study consisting of three 3-week phases in 10 adults with PKU: phase 1 (washout), phase 2 (supplementation of large neutral amino acid [LNAA] tablets or placebo), and phase 3 (alternate supplementation). An overnight protocol to measure blood melatonin and urine 6-sulfatoxymelatonin and dopamine in first void urine specimens was conducted after each phase for subjects with PKU and once in 10 controls.
resultsSignificantly lower concentrations of these neurotransmitter metabolites were observed in subjects with PKU after phase 1 compared with controls (serum melatonin P = .008, urine melatonin P = .0043, urine dopamine P < .0001), with significant increases after LNAA supplementation compared with the placebo phase (serum melatonin P = .0008, urine melatonin P = .0008, urine dopamine P = .0005). The mean tryptophan/LNAA and tyrosine/LNAA ratios were markedly lower in subjects with PKU compared with controls, and these ratios were significantly increased in the LNAA phase compared with the placebo phase (P = .016, P = .0003, respectively). Blood phenylalanine levels in subjects with PKU were not significantly different between placebo and LNAA phases (P = .74).
conclusionBlood and urine melatonin levels may serve as biomarkers reflecting brain serotonin synthesis in subjects with PKU. Because this cannot be evaluated using blood phenylalanine levels, it may provide information on neurotransmitter metabolism for optimal dietary management.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.