University of Wisconsin–Madison

Denise Ney, PhD – Slide of the Week

Denise Ney Slide of the Week

Title: Metabolomics of Carnitine Metabolism in Participants with Phenylketonuria with the Use of AA and GMP Medical Foods

Legend: Intake of dietary cholesterol (A) and metabolomics of cholesterol metabolism (B, C). Values are scaled intensity means ± SEM for metabolites in plasma (Classical PKU, n=5; Variant PKU, n=5; Controls, n=15). Values for dietary intake are means ± SEM. Total dietary cholesterol intakes are based on 3-d food records, (Classical PKU, n=20; Variant PKU, n=10). Labeled means without a common letter differ, P<0.05. AA-MF, amino acid medical foods; GMP-MF, glycomacropeptide medical foods; PKU, phenylketonuria.

Citation: Stroup BM, Nair N, Murali SG, Broniowska K, Rohr F, Levy HL, Ney DM. (2018). Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria. Journal of Nutrition, 1;148(2):194-201.

Abstract: Background – Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (MFs). Objective – To assess lipid metabolism in participants with PKU consuming amino acid MFs (AA-MFs) or glycomacropeptide MFs (GMP-MFs), we conducted fatty acid and metabolomics analyses. Methods – We used subsets of fasting plasma and urine samples from our randomized crossover trial in which participants with early-treated classical and variant (milder) PKU consumed a low-Phe diet combined with AA-MFs or GMP-MFs for 3 weeks each. Fatty-acid profiles of red blood cell (RBC) membranes were determined for 25 adults (aged 18-49 years) with PKU and 143 control participants. Metabolomics analyses of plasma and urine samples were conducted by Metabolon for 9-10 adolescent and adult participants with PKU and for 15 control participants. Results – RBC fatty acid profiles were not significantly different with AA-MFs or GMP-MFs. PKU participants showed higher total n-6:n-3 (ω-6:ω-3) fatty acids (mean ± SD percentages of total fatty acids: AA-MF = 5.45% ± 1.07%; Controls = 4.33%; P < 0.001) and lower docosahexaenoic acid (DHA; AA-MF = 3.21% ± 0.98%; Controls = 3.70% ± 1.01%; P = 0.02) and eicosapentaenoic acid (AA-MF = 0.33% ± 0.12%; Controls = 0.60% ± 0.43%; P < 0.001) in RBCs than did control participants. Despite higher carnitine intake from AA-MFs than GMP-MFs (mean ± SE intake: AA-MFs = 58.6 ± 5.3 mg/d; GMP-MFs = 0.3 ± 0.01 mg/d; P < 0.001), plasma concentrations of carnitine were similar and not different from those in the control group (AA-MF compared with GMP-MF, P = 0.73). AA-MFs resulted in higher urinary excretion of trimethylamine N-oxide (TMAO), which is synthesized by bacteria from carnitine, compared with GMP-MFs (mean ± SE scaled intensity-TMAO: AA-MFs = 1.2 ± 0.1, GMP-MFs = 0.9 ± 0.1; P = 0.005). Plasma deoxycarnitine was lower in PKU participants than in control participants, suggesting reduced carnitine biosynthesis in PKU (AA-MF = 0.9 ± 0.1; GMP-MF = 1.0 ± 0.1; Controls = 1.3 ± 0.1; AA-MF compared with controls, P = 0.01; GMP-MF compared with controls, P = 0.04). Conclusions – Supplementation with DHA is needed in PKU. Carnitine supplementation of AA-MFs shows reduced bioavailability due, in part, to bacterial degradation to TMAO, whereas the bioavailability of carnitine is greater with prebiotic GMP-MFs. This trial was registered at as NCT01428258.

About the Lab: The Ney research group has conducted studies in individuals with PKU that establishes the acceptability and safety of foods made with the whey protein, glycomacropeptide, in the nutritional management of PKU, a genetic disorder caused by deficiency of the hepatic enzyme phenylalanine hydroxylase that converts the essential amino acid phenylalanine to tyrosine. To prevent brain damage and cognitive impairment, individuals with PKU must follow a lifelong, low-phenylalanine diet that is restricted in natural foods and requires ingestion of a bitter-tasting amino acid formula. Glycomacropeptide (GMP) is uniquely suited to the PKU diet because it is the only known dietary protein that contains only trace amounts of phenylalanine. Low-phenylalanine food products made from GMP provide a palatable and acceptable alternative to the amino acid formulas currently required in the PKU diet.

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