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

Hans Demmelmair, Anita MacDonald, Urania Kotzaeridou, Peter Burgard, Domingo Gonzalez-Lamuno, Elvira Verduci, Melike Ersoy, Gulden Gokcay, Behiye Alyanak, Eva Reischl, Wolfgang Müller-Felber, Fabienne Lara Faber, Uschi Handel, Sabrina Paci, Berthold Koletzko

Journal: Nutrients 2019;10(12):1944

PMID: 30544518

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Abstract

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.

Address: Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany. [email protected].; The Children's Hospital Birmingham, Birmingham B4 6NH, UK. [email protected].; Division of Neuropediatrics and Metabolic Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany. [email protected].; Division of Neuropediatrics and Metabolic Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany. [email protected].; Department of Pediatrics, IDIVAL-Hospital M. Valdecilla, 39008 Santander, Spain. [email protected].; Department of Pediatrics, San Paolo Hospital Milano, 20142 Milano, Italy. [email protected].; Department of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, Turkey. [email protected].; Department of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, Turkey. [email protected].; Department of Child Psychiatry, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, Turkey. [email protected].; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany. [email protected].; Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany. [email protected].; Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany. [email protected].; Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany. [email protected].; Department of Pediatrics, San Paolo Hospital Milano, 20142 Milano, Italy. [email protected].; Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany. [email protected].

DOI: 10.3390/nu10121944

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MeSH Terms: Adolescent, Child, Cognition, Docosahexaenoic Acids, Fatty Acid Desaturases, Female, Humans, Male, Motor Skills, Phenylketonurias