Nutritional issues and impact of treatment in patients with phenylketonuria

Alfheeaid, Hani A. (2018) Nutritional issues and impact of treatment in patients with phenylketonuria. PhD thesis, University of Glasgow.

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Abstract

In the early days of PKU, micronutrient deficiencies, undernutrition and growth failure were common features of patients with the condition. This was mainly due to the limited availability of engineered special low protein foods (SLPF) and PKU protein substitutes to use. Nowadays, SLPF foods and micronutrient-enriched PKU protein substitutes have become widely available and are free on prescription in most countries. These SLPF are high in carbohydrates and often in fat content, have a higher glycaemic index and provide more energy per weight compared with the protein-containing equivalent normal foods.
Advancement in the PKU management, including dietary practices, led to nutritional problems that had never been reported before, but have become more frequent in the recent years. Overweight and obesity, rather than undernutrition, have become increasingly reported in patients with PKU, with some studies suggesting higher prevalence in females than males. Data on body composition in patients with PKU are inconsistent with some studies showing that patients with PKU have higher FM and lower FFM compared to healthy controls. This suggests that for a given body weight and height, patients with PKU might be fatter and look bigger. However, there is very little research looking at the determinants of nutrient status, body composition and obesity in patients with PKU.
Hence, among the aims of this thesis was to investigate the impact of a PKU SLPF-based meal on appetite ratings, gut appetite hormones, thermic effect of feeding (TEF) and fat oxidation (Chapter 2). Twenty-three healthy adults (mean ± SD age: 24.3 ± 5.1 years; BMI: 22.4 ± 2.5 kg/m2) participated in a randomised crossover study. Each participant conducted two (PKU and Control) experimental trials which involved consumption of a PKU SLPF-based meal and protein substitute drink or an isocaloric and weight matched ordinary meal and protein-enriched milk drink. Appetite, metabolic rate, fat oxidation measurements and blood collections were conducted for the duration of 300 minutes. On completion of the measurements, an ad libitum buffet dinner was served. Responses of appetite ratings, plasma concentrations of GLP-1 and PYY (P>0.05, trial effect, two-way ANOVA) and energy intake during ad libitum buffet dinner (P>0.05, paired t-test) were not significantly different between the two trials. The TEF (PKU, 10.2 ±1.5%; Control, 13.2 ± 1.0%) and the total amount of fat oxidised (PKU, 18.90 ± 1.10 g; Control, 22.10 ± 1.10 g) were significantly (P<0.05, paired t-tests) lower in the PKU than in the Control trial. The differences in TEF and fat oxidation were significant (P<0.05, paired t-tests) for the post-meal period. Therefore, from this first study we concluded that consumption of a meal composed of SLPF has no detrimental impact on appetite and appetite hormones but produces a lower TEF and postprandial fat oxidation than an ordinary meal. We hypothesised that these metabolic alterations may contribute to the increased prevalence of obesity reported in patients with PKU on contemporary dietary management.
In the second experimental chapter, we tested the hypothesis generated from the study above and measured TEF, fasting and postprandial fat and CHO oxidation in 13 patients with PKU and 10 healthy controls of similar age and BMI. Participants in the PKU group were provided an SLPF-based meal while those in the Control group were provided an isocaloric normal meal. It was found that TEF, and postprandial fat and CHO oxidation were not signifcantly different between the PKU and the Control groups. In addition, this study compared body composition characteristics (measured by Deuterium Oxide dilution technique) between PKU patients and healthy controls and revealed that differences in body composition are not significant between the two groups despite a tendency of PKU patients having higher percentage of body fatness (P=0.08). However, data generated from this study should be interpreted with caution and requires confirmation from studies with larger sample size.
Micronutrient imbalance has been noted in patients with PKU despite their high provision through the PKU protein substitutes. Recent studies showed high blood levels of vitamin B12 and folate, but simultaneously deficient plasma levels of selenium and zinc in PKU patients prescribed with micronutrient-enriched PKU protein substitutes. Factors associated with micronutrient imbalance have rarely been studied in the literature. Therefore, the last chapter of this thesis aimed to evaluate the micronutrient status of children with PKU and explore factors associated with micronutrient imbalances and deficiencies. This was analysis of a large clinical dataset with serial measurements obtained from PKU children (≤16 years) attending the metabolic medicine clinic at the Glasgow Royal Hospital for Sick Children between 1990 and 2013. The study included 81 patients who provided a total of 512 blood samples for their routine annual micronutrient screening. Data on blood micronutrient measurements was available for vitamins A, B12, D, E, serum folate, and erythrocyte folate and the trace elements copper, selenium, zinc and serum ferritin as a biomarker of iron stores. Status of vitamin B12, E, and serum and erythrocyte folate measurements were above the normal range (NR) in 27%, 54%, 46% and 35% of the blood samples, respectively. However, 44% of selenium and 14% of zinc measurements were below the NR. Moreover, when we compared results with those from the UK National Dietary and Nutritional Survey, selenium and zinc deficiencies were specific to PKU condition and not a reflection of the epidemiology in the general UK population. In our PKU sample, poor metabolic control, PKU severity, and low adherence to PKU protein substitutes predicted low selenium status; while deficient zinc status was solely predicted by low adherence to PKU protein substitutes. Yet, these predictors, collectively, explained a small (5.8 – 8.8 %) variation in the status of selenium and zinc in this group of patients. Selenium and zinc deficiencies are common in PKU patients despite high levels of other nutrients including vitamin B12, E and folate. The findings of this study suggest that selenium and zinc deficiencies reported in patients with PKU may be attributed to other factors which we were unable to measure in this retrospective study, such as low bioavailability of these nutrients from the artificial PKU protein substitutes.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: A chapter of this thesis has been published in Clinical Nutrition Journal: PMID: 28318688 DOI: 10.1016/j.clnu.2017.03.005
Keywords: Clinical nutrition, dietetics, nutrition therapy, PKU, genetic disorder, phenylalanine, hyperphenylalaninemia, metabolic, thermogenesis, fat oxidation, low protein diet, appetite, energy balance, obesity, protein substitutes, micronutrients, vitamins, trace elements, deficiency.
Subjects: R Medicine > R Medicine (General)
R Medicine > RB Pathology
R Medicine > RZ Other systems of medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Supervisor's Name: Gerasimidis, Dr. Konstantinos and Dalia, Dr. Malkova
Date of Award: 2018
Embargo Date: 3 April 2023
Depositing User: Dr HA Alfheeaid
Unique ID: glathesis:2018-8938
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 05 Apr 2018 14:24
Last Modified: 10 May 2018 06:59
URI: http://theses.gla.ac.uk/id/eprint/8938
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