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Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study

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Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children’s Hospital, 80337 Munich, Germany
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The Children’s Hospital Birmingham, Birmingham B4 6NH, UK
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Division of Neuropediatrics and Metabolic Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany
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Department of Pediatrics, IDIVAL-Hospital M. Valdecilla, 39008 Santander, Spain
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Department of Pediatrics, San Paolo Hospital Milano, 20142 Milano, Italy
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Department of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, Turkey
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Department of Child Psychiatry, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, Turkey
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Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany
*
Authors to whom correspondence should be addressed.
Nutrients 2018, 10(12), 1944; https://doi.org/10.3390/nu10121944
Received: 5 October 2018 / Revised: 7 November 2018 / Accepted: 30 November 2018 / Published: 7 December 2018
(This article belongs to the Special Issue DHA and Neurocognitive Function)
Children with phenylketonuria (PKU) follow a protein restricted diet with negligible amounts of docosahexaenoic acid (DHA). Low DHA intakes might explain subtle neurological deficits in PKU. We studied whether a DHA supply modified plasma DHA and neurological and intellectual functioning in PKU. In a double-blind multicentric trial, 109 PKU patients were randomized to DHA doses from 0 to 7 mg/kg&day for six months. Before and after supplementation, we determined plasma fatty acid concentrations, latencies of visually evoked potentials, fine and gross motor behavior, and IQ. Fatty acid desaturase genotypes were also determined. DHA supplementation increased plasma glycerophospholipid DHA proportional to dose by 0.4% DHA per 1 mg intake/kg bodyweight. Functional outcomes were not associated with DHA status before and after intervention and remained unchanged by supplementation. Genotypes were associated with plasma arachidonic acid levels and, if considered together with the levels of the precursor alpha-linolenic acid, also with DHA. Functional outcomes and supplementation effects were not significantly associated with genotype. DHA intakes up to 7 mg/kg did not improve neurological functions in PKU children. Nervous tissues may be less prone to low DHA levels after infancy, or higher doses might be required to impact neurological functions. In situations of minimal dietary DHA, endogenous synthesis of DHA from alpha-linolenic acid could relevantly contribute to DHA status. View Full-Text
Keywords: phenylketonuria; docosahexaenoic acid; cognitive function; motor skills; neurological function phenylketonuria; docosahexaenoic acid; cognitive function; motor skills; neurological function
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Demmelmair, H.; MacDonald, A.; Kotzaeridou, U.; Burgard, P.; Gonzalez-Lamuno, D.; Verduci, E.; Ersoy, M.; Gokcay, G.; Alyanak, B.; Reischl, E.; Müller-Felber, W.; Faber, F.L.; Handel, U.; Paci, S.; Koletzko, B. Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study. Nutrients 2018, 10, 1944.

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