Metabolomics of Dietary Fatty Acid Restriction in Patients with Phenylketonuria

Abstract

BackgroundPatients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA). Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here.Methodology/Principal Findings12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6–C18) in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS). Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re-) absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6) a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B2 and thromboxane B3 release did not differ from that of healthy controls.Conclusion/SignificanceLong-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta-oxidation. No functional influence on unsaturated fatty acid metabolism and platelet aggregation in patients with PKU was detected.

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients

“…Second, phenylketonuria patients generally consume a vegetarian diet, especially well-controlled patients who strictly comply with this low-cholesterol diet. 8,22 Our results support this hypothesis. Numerous studies have shown that people consuming vegetarian and also vegan diet had lower high-density lipoprotein cholesterol levels compared with omnivorous healthy people.…”

“…There are few studies that have investigated the known risk factors of atherosclerosis, such as blood lipids, homocysteine, and mean platelet volume in phenylketonuria patients, in the literature. 3,[6][7][8][9][14][15][16][17][18][19][20][21][22] In most of these previous studies, these factors were evaluated independently, and only one of them included mean platelet volume levels. 22 The primary aim of the present study was to investigate the serum atherogenic markers in adolescent phenylketonuria patients and compare these parameters with healthy peers.…”

Dietary treatment in phenylketonuria does not lead to increased risk of obesity or metabolic syndrome

“…Our data indicate that better compliance with the diet may be associated with a reduced prevalence of overweight and obesity. PKU patients have a low-protein diet which is comparable to a vegetarian diet [34], leading to less fatty acid intake [35] and more contribution of carbohydrates in order to complete their energetic needs [36]. Our data, regarding nutritional intake seems to be in accordance with this statement, showing relatively low fat intake but huge contribution from carbohydrates compared with Portuguese non-PKU population [37].…”

Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria

“…DHA and EPA are known to have cardio-protective effects [43] and deficiencies may lead to CNS disease or affect the immune system [42]. Normal as well as reduced plasma and erythrocyte FA levels have been reported in patients with PKU [44,45,46,47,48,49]. It is, however, not clear what these deficiencies mean and if they have a clinical impact on the patients.…”