Does meal-time insulin dosing based on fat-protein counting give positive results in postprandial glycaemic profile after a high protein-fat meal in adolescents with type 1 diabetes: a randomised controlled trial.

BACKGROUND: The present study investigated the effects of fat-protein (CFP) counting in addition to carbohydrate (CARB) counting for calculating prandial insulin dosage on blood glucose profile in patients with type 1 diabetes (T1D) on basal-bolus insulin therapy. METHODS: In this single centre, cross-over, randomised, controlled study, control meal (SM: standard meal using a carbohydrate counting method) and three test meals (HPM: high protein meal using a carbohydrate counting method; HPFM-a: high protein-fat meal using a carbohydrate counting method; HPFM-b: high protein-fat meal using a carbohydrate and fat-protein counting method) were compared on postprandial early (0-120 min), late (120-240 min) and total (0-240 min) glucose response in 30 patients with T1D, aged 16-18 years. RESULTS: The glucose levels of 0-90 min did not change after different meal consumptions (P > 0.05), whereas 120-240 min glucose levels were higher after HPFM-a consumption compared to HPFM-b consumption (P < 0.05). There were no significant differences between meals with respect to the early postprandial glucose response (0-120 min) (P = 0.405). In late response (120-240 min), HPFM-b [area under the curve (AUC) = 20 609 (582) mg dL-1  × dk] was significantly lower than SM [AUC = 24 092 (9015) mg dL-1  × dk], HPM [AUC = 24 072 (5853) mg dL-1  × dk] and HPFM-a [AUC = 25 986 (6979) mg dL-1  × dk] (P = 0.032). CONCLUSIONS: Meal-related insulin dosing based on carbohydrate plus fat/protein counting has given positive results in the postprandial glycaemic profile as a result of lower postprandial glycaemic levels compared to conventional carbohydrate counting in patients with T1D after a high protein-fat meal.

Does food insulin index in the context of mixed meals affect postprandial metabolic responses and appetite in obese adolescents with insulin resistance? A randomised cross-over trial.

The food insulin index (II) is a novel classification to rank foods based on their physiological insulin demand relative to an isoenergetic reference food and may be a valid predictor of postprandial insulin responses and appetite. The present study aimed to compare the postprandial metabolic responses and appetite sensations to two macronutrient- and glycaemic index-matched meals with either high or low II in obese adolescents with insulin resistance (IR). A randomised, single-blind and cross-over trial included fifteen obese adolescents aged 12-18 years with IR. All participants were provided with two different breakfasts: low glycaemic index, low insulin index (LGI-LII) and low glycaemic index, high insulin index (LGI-HII), with a 1-week washout period between meals. At time 0 (just before breakfast), 15, 30, 45, 60, 90, 120, 180 and 240 min after the meal, serum glucose, insulin and C-peptide levels and appetite scores were measured. At the end of 4 h, participants were served ad libitum lunch. Early (0-30 min), late (45-240 min) and total (0-240 min) postprandial insulin responses were lowered by 56·1, 34·6 and 35·6 % after the LGI-LII meal v. LGI-HII meal (P < 0·05). The feeling of hunger was also decreased by 25·8 and 27·5 % after the LGI-LII meal v. LGI-HII meal during the late and total responses (P < 0·05). The calculation II of meals or diets may be a useful dietary approach to reduce postprandial hyperinsulinaemia and the perceived hunger in obese adolescents with IR.

Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Protein substitutes for phenylketonuria in Europe: access and nutritional composition.

BACKGROUND/OBJECTIVES: Protein substitutes (PS) are an essential component in the dietary management of phenylketonuria (PKU). PS are available as phenylalanine-free amino-acid mixtures (AAM), glycomacropeptide-based PS (GMP) and large neutral amino acids (LNAA). There is a lack of information regarding their availability in different countries and comparison of their nutritional composition is limited. The objectives of this study were to identify the number of PS available in different European countries and Turkey and to compare their nutritional composition. SUBJECTS/METHODS: Members of the European Nutritionist Expert Panel on PKU (ENEP) (Portugal, Spain, Belgium, Italy, Germany, Netherlands, United Kingdom, Denmark and Turkey) provided data on PS available in each country. The nutritional composition of PS available in Portugal was analyzed. RESULTS: The number of PS available in each country varied from 30 (Turkey) to 105 (Germany), with a median of 64. GMP was available only in Portugal, whereas LNAA was an option in Portugal, Italy, Turkey and Denmark. Some PS were designed for weaning. Many PS did not contain added fat and fiber. GMP contained the highest carbohydrate (CHO) and energy content as well as higher LNAA content compared with AAM. Only one AAM contained added fructo-oligosaccharides and galacto-oligosaccharides. AAM designed for the first year of life had the highest CHO, fat and LNAA contribution. Liquid AAM had lower CHO and fat contents compared with powdered AAM, but contained higher LNAA. CONCLUSIONS: There was widely dissimilar numbers of PS available in different countries. Nutritional composition of different PS was variable and should be considered before prescription.

The challenges of managing coexistent disorders with phenylketonuria: 30 cases.

INTRODUCTION: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study. METHODS: Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported. RESULTS: 30 patients (11 males and 19 females), with PKU and a co-existent condition, current median age of 14 years (range 0.4 to 40 years) from 13 treatment centres from Europe and Turkey were described. There were 21 co-existent conditions with PKU; 9 were autoimmune; 6 gastrointestinal, 3 chromosomal abnormalities, and 3 inherited conditions. There were only 5 cases of parental consanguinity. Some patients required conflicting diet therapy (n=5), nutritional support (n=7) and 5 children had feeding problems. There was delayed diagnosis of co-existent conditions (n=3); delayed treatment of PKU (n=1) and amenorrhea associated with Grave's disease that masked a PKU pregnancy for 12 weeks. Co-existent conditions adversely affected blood Phe control in 47% (n=14) of patients. Some co-existent conditions increased the complexity of disease management and increased management burden for patients and caregivers. CONCLUSIONS: Occurrence of co-existent disease is not uncommon in patients with PKU and so investigation for co-existent disorders when the clinical history is not completely consistent with PKU is essential. Integrating care of a second condition with PKU management is challenging.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Overweight and obesity in PKU: The results from 8 centres in Europe and Turkey.

INTRODUCTION: In PKU there is little data comparing the prevalence of overweight and obesity in different countries. The aim of this cross sectional study was to evaluate prevalence data from different PKU treatment centres in Europe and Turkey. SUBJECTS AND METHODS: In children, body mass index (BMI) and z scores and in adults BMI were calculated in 947 patients (783 children aged < 19 years; 164 adults aged ≥ 19 years) with PKU from centres in Europe and Turkey (Ankara, Birmingham, Brussels, Copenhagen, Groningen, Madrid, Munich and Porto). RESULTS: In adults with PKU, 83% of centres (n = 5/6) had less overweight than the general populations but 83% (n = 5/6) had a higher rate of female obesity. In childhood, all centres reported obesity rates within or similar to local population ranges in boys but in 57% (n = 4/7) of centres a higher rate of obesity in girls. The percentage of overweight and obesity increased with age. DISCUSSION: In PKU, it is clear from a number of treatment centres that women and girls with PKU appear particularly vulnerable to excess weight gain and it is important that female weight gain is closely monitored and individual strategies introduced to prevent excess weight gain. Overall, in PKU there is a need to understand better the food patterns and activity levels of patients.

Micronutrient status in phenylketonuria.

Patients with phenylketonuria (PKU) encompass an 'at risk' group for micronutrient imbalances. Optimal nutrient status is challenging particularly when a substantial proportion of nutrient intake is from non-natural sources. In PKU patients following dietary treatment, supplementation with micronutrients is a necessity and vitamins and minerals should either be added to supplement phenylalanine-free l-amino acids or given separately. In this literature review of papers published since 1990, the prevalence of vitamin and mineral deficiency is described, with reference to age of treatment commencement, type of treatment, dietary compliance, and dietary practices. Biological micronutrient inadequacies have been mainly reported for zinc, selenium, iron, vitamin B12 and folate. The aetiology of these results and possible clinical and biological implications are discussed. In PKU there is not a simple relationship between the dietary intake and nutritional status, and there are many independent and interrelated complex factors that should be considered other than quantitative nutritional intake.

Use of sapropterin in the management of phenylketonuria: seven case reports.

Sapropterin treatment, with or without dietary treatment, improves blood phenylalanine control, increases phenylalanine tolerance, and may reduce the day-to-day dietary treatment burden in a subset of patients with phenylketonuria (PKU). Balancing the need for maintained control of blood phenylalanine with diet relaxation is complex when administering sapropterin. We present a series of seven patient cases with PKU that illustrate important aspects of using sapropterin with diet in the management of the disorder.

Dietary practices in glutaric aciduria type 1 over 16 years.

BACKGROUND: In glutaric aciduria type 1 (GA1), dietary treatment with emergency management (EM) is essential to prevent encephalopathic crisis (EC). In the present study, dietary practices were examined in a single UK centre without access to newborn screening. METHODS: Twenty GA1 patients (11 males, median age: 10.2 years, range 2.2-24.1 years) were evaluated. Nine presented without EC (median diagnosis age: 1.1 years, range 4 days to 8 years) and 11 with EC (median diagnosis age 10 months, range 6 months to 1.7 years). Dietary treatment, neurological outcome, anthropometry and biochemical/haematological markers were assessed. RESULTS: Diet treatment varied according to age of diagnosis and symptom severity. Four of six pre-encephalopathic children diagnosed before 2 years of age were treated with carnitine, protein restriction (medium l.2 g kg day(-1)) and lysine-free/low tryptophan protein substitute (PS) (medium dose: 1.6 g kg day(-1)). EM consisted of natural protein cessation and glucose polymer with PS delivered via an enteral feeding tube. Older children (>3 years) without EC were given carnitine and protein restriction, and seven of nine EC patients had PS via an enteral feeding tube. Clinical deterioration occurred in two patients without EC; one taking PS and protein restriction (with a second untreatable pathology) and one after protein restriction only. In patients presenting with EC, four died and one had some improvement in movement, with the rest remaining stable but with severe disability. Patients taking PS had better nutritional markers [serum vitamin B(12) (P < 0.001), albumin (P < 0.001), haemoglobin (P < 0.001) and essential plasma amino acids]. CONCLUSIONS: Early diagnosis of GA1 before EC is essential because PS and protein restriction with meticulous EM prevents EC. PS also improves nutritional status irrespective of clinical condition.

Diet in phenylketonuria: a snapshot of special dietary costs and reimbursement systems in 10 international centers.

BACKGROUND AND AIMS: To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers. METHODS: Experts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients. RESULTS: The mean annual cost of protein substitutes across 4 age groups (2 y, 8 y, 15 y and adults) ranged from €4273 to €21,590 per patient. The cost of low-protein products also differed; the mean cost of low-protein bread varied from €0.04 to €1.60 per 100 kcal. All protein substitutes were either fully reimbursed or covered by health insurance. However, reimbursement for low-protein products varied and state benefits differed between centers. CONCLUSIONS: The variation in the cost and reimbursement of diet therapy and the level of additional state benefits for PKU patients demonstrates the large difference in expenditure on and access to PKU dietary products. This highlights the inequality between healthcare systems and access to special dietary products for people with PKU, ultimately leading to patients in some countries receiving better care than others.

Diurnal variation of phenylalanine concentrations in tyrosinaemia type 1: should we be concerned?

BACKGROUND: Tyrosinaemia type 1 (HT1) is treated with a tyrosine and phenylalanine-restricted diet, amino acids free of phenylalanine and tyrosine, and nitisinone (NTBC). Treatment guidelines recommend plasma tyrosine between 200-400 µm and phenylalanine at least >30 µm. There is little information on the diurnal variation of plasma tyrosine or phenylalanine in HT1. Low plasma phenylalanine <30 µm may be associated with poor growth and cognitive delay. The present study aimed to document diurnal variation of tyrosine and phenylalanine plasma concentrations and growth in children with HT1. METHODS: Median tyrosine and phenylalanine plasma concentrations were reviewed retrospectively over 3 years in 11 subjects (median age 4 years) with HT1. Subjects routinely collected morning fasting blood samples but afternoon nonfasted samples were taken in the clinic (<10% of samples). Growth Z-scores were calculated. RESULTS: The percentage of all plasma phenylalanine concentrations <30 µm was 8.6% and <40 µm was 13.6%. Only 2% of fasting morning phenylalanine concentrations were <30 µm, compared to 83% of nonfasting afternoon samples. All but one child had a height Z-score <0. CONCLUSIONS: Blood phenylalanine concentrations were consistently lower in the afternoon. Taking blood samples at variable time points in the day may lead to variation in interpreting dietary control. A detailed study is necessary to examine the 24-h diurnal variation of plasma phenylalanine and tyrosine in HT1. It is possible that phenylalanine concentrations may be very low for a substantive time over 24 h and the potential impact that this may have on cognitive development and growth in children is unknown.

The development of nonweighed pilot methods for estimating phenylalanine exchanges in non-phenylketonuria volunteers.

BACKGROUND: In children with phenylketonuria (PKU), the daily weighing of the phenylalanine allowance from food is advocated. There is a need to develop nonweighed methods of measuring dietary phenylalanine, aiming to ease caregiver burden and possibly improve dietary adherence. The accuracy of three methods (household measures, digital photographs and weighing) for measuring 50-mg phenylalanine exchanges for PKU was investigated in a randomised, controlled trial. METHODS: There were 51 volunteers (32 females; 19 males; median age: 34years, range 13-77years), who were all unconnected with PKU. For three consecutive days, all volunteers attended a research centre and, each day, were randomly allocated a different method (household measures, digital photographs and weighing) for phenylalanine exchange measurement. On each day, they measured the amount of food equivalent to one 50-mg phenylalanine exchange for 24 common foods. All phenylalanine exchange samples (3672 samples) were then reweighed by the investigators. RESULTS: No method of measuring 50-mg phenylalanine exchanges was accurate when used by volunteers. The median percentages (range) of all food samples within 10% of target were only 67% (41-98), 44% (4-96) and 41% (4-98) for weighing, household measures and photographs, respectively. The respective median (range) of samples within 20% of the target weights were: 96% (51-100) weighing, 82% (10-100) photographs and 80% (6-100) household measures. No noteworthy difference in accuracy was observed between household measures and photographs. CONCLUSIONS: Volunteers not associated with PKU could not measure 50-mg phenylalanine exchanges accurately using weighing, household measurements or photographs. Therefore, it is important to consider developing methods for improving accuracy of measurement of 50-mg phenylalanine exchanges in PKU.

Blood phenylalanine control in phenylketonuria: a survey of 10 European centres.

BACKGROUND: Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet. OBJECTIVE: A survey was conducted to compare blood Phe control achieved in diet-treated patients with PKU of different age groups in 10 European centres. METHODS: Centres experienced in the management of PKU from Belgium, Denmark, Germany, Italy, The Netherlands, Norway, Poland, Spain, Turkey and the United Kingdom provided retrospective audit data of all patients with PKU treated by diet over a 1-year period. Standard questions were used to collect median data on blood Phe concentrations, percentage of blood Phe concentrations below upper target reference ranges and frequency of blood Phe sampling. RESULTS: Data from 1921 patients on dietary management were included. Blood Phe concentrations were well controlled and comparable across centres in the early years of life. The percentages of blood Phe concentrations meeting each centre's local and national target ranges were 88% in children aged up to 1 year, 74% for 1-10 years, 89% for 11-16 years and 65% for adults (>16 years). The frequency of home blood sampling, compared with local and national recommendations for monitoring Phe concentrations, appeared to decline with age (from approximately 100% in infancy to 83% in teenagers and 55% in adults). CONCLUSIONS: Although blood Phe control generally deteriorated with age, some improvement was observed in adolescent years across the 10 European centres. The blood Phe control achieved seemed comparable in many of the European centres irrespective of different dietary treatments or national policies.

Errors in emergency feeds in inherited metabolic disorders: a randomised controlled trial of three preparation methods.

OBJECTIVE: Glucose polymer-based emergency feeds (EF), used during illness to prevent metabolic decompensation and encephalopathy in inherited metabolic disorders, should be produced accurately and safely. DESIGN: In a randomised, prospective, controlled study, the aim was to investigate if when preparing age-appropriate EF, a pre-measured sachet of glucose polymer, compared with scoops and weighing (using digital scales), decreased carer errors. SUBJECTS: 47 carers (3 men, 44 women) of 52 inherited metabolic disorders patients were recruited. SETTING AND INTERVENTION: The carers made EF using all three techniques (weighing, scoops and pre-measured sachets) under supervision in controlled and home conditions. A 100-ml aliquot of each EF was analysed for carbohydrate concentration. RESULTS: Under controlled preparation conditions, with 1 litre EFs, the % median glucose polymer concentration closest to target amounts was (1) pre-measured sachets (105%), (2) weighing (107%) and (3) scoops (118%; p<0.001). Similarly, under home conditions, the closest method was (1) pre-measured sachets (111%), (2) weighing (112%) and (3) scoops (118%; p<0.05). Under home preparation conditions, with 200 ml EFs, the pre-measured sachets were more likely to be within 20% of target weight than weighing (p<0.05), but there was no difference with scoops. Common errors observed were inaccurate water measurements (40% controlled and home conditions), incorrect scoop measurements and difficulty using digital scales. CONCLUSIONS; Overall, using pre-measured sachets was more accurate in EF production. Pre-measured sachets are likely to decrease preparation error and, therefore, reduce the risk of feed intolerance, particularly osmotic diarrhoea and consequential metabolic decompensation and encephalopathy.

Long-term efficacy of 'ready-to-drink' protein substitute in phenylketonuria.

BACKGROUND: In phenylketonuria (PKU), protein substitute is an essential part of dietary treatment. Short-term studies have demonstrated that liquid protein substitutes (LPS) are efficacious, and improve compliance in teenagers and adults with PKU, although there are no data available to demonstrate that their effectiveness is sustained over time. The present retrospective study aimed to evaluate the long-term efficacy of ready-to-drink protein substitute in a group of people with PKU. METHODS: Thirty-four patients (17 females and 17 males, median age 14.9 years, range 7.2-53.8 years) with PKU on dietary management were recruited from Birmingham Children's Hospital. All patients who were taking a LPS for a median of 2.4 years (range 6 months to 4.1 years), had their plasma phenylalanine concentrations, anthropometric and nutritional biochemical markers reviewed, both before and when taking the LPS. RESULTS: There was a significant improvement in median plasma phenylalanine (P < 0.05), vitamin B(12) (P < 0.01), calcium (P < 0.05) and albumin (P < 0.05) concentrations in subjects (n = 13) aged >18 years when taking the LPS. In the children aged 7-18 years (n = 21), median plasma phenylalanine concentrations were maintained on LPS. Their plasma selenium concentrations (P < 0.05) deteriorated, but calcium (P < 0.05), albumin (P < 0.01), haemoglobin (P < 0.01) and haematocrit (P < 0.01) significantly improved. CONCLUSIONS: This retrospective review suggested that, in adult patients, the long-term use of LPS is associated with better compliance by lowering blood phenylalanine and improving nutritional biochemical markers.

Long-term compliance with a novel vitamin and mineral supplement in older people with PKU.

BACKGROUND: The long-term efficacy of vitamin and mineral preparations in dietary-treated adult patients with phenylketonuria (PKU) is unreported. AIM: In an open, intervention trial, the acceptability, safety and impact on biochemical and haematological micronutrient status of a new vitamin and mineral tablet (Phlexy Vits, SHS International) was investigated. METHODS: Fifteen subjects with PKU (median age 21 years, range 8-33 years) on low-phenylalanine diet from two PKU centres were recruited. No vitamins or minerals were added to their protein substitute and for 12 months they took their full daily requirements of vitamin and minerals from Phlexy Vits (5 tablets/daily). All but two subjects had taken alternative vitamin and mineral supplements before the trial. Fasting bloods were taken at baseline (week -2 and at week 0), 4 and 12 months for a range of biochemical and nutritional measurements. RESULTS: By 4 months, serum vitamin B(12) (p = 0.003), serum manganese (p=0.03) and plasma (p=0.03) and red blood cell (p=0.004) glutathionine peroxidase (GSHPx) all significantly increased but remained within normal reference ranges. By 12 months, serum vitamin B(12) (p<0.05) and plasma GSHPx (p<0.05) remained increased. The Phlexy Vits tablets scored better than conventional vitamin and mineral supplements for overall acceptability (p<0.05), and ease of swallowing (p=0.1) at 4 months, although swallowing score deteriorated by 12 months (p<0.05). There was a small but significant deterioration in compliance with taking the vitamin and mineral supplements between 4 and 12 months (p<0.05). CONCLUSION: In the long term, these comprehensive vitamin and mineral tablets appeared acceptable and improved biochemical nutritional status, although there were long-term compliance and swallowing issues.