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1.
Nutrients ; 13(9)2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34579102

RESUMEN

Tyrosinemia type I (HTI) is treated with nitisinone, a tyrosine (Tyr) and phenylalanine (Phe)-restricted diet, and supplemented with a Tyr/Phe-free protein substitute (PS). Casein glycomacropeptide (CGMP), a bioactive peptide, is an alternative protein source to traditional amino acids (L-AA). CGMP contains residual Tyr and Phe and requires supplementation with tryptophan, histidine, methionine, leucine, cysteine and arginine. AIMS: a 2-part study assessed: (1) the tolerance and acceptability of a low Tyr/Phe CGMP-based PS over 28 days, and (2) its long-term impact on metabolic control and growth over 12 months. METHODS: 11 children with HTI were recruited and given a low Tyr/Phe CGMP to supply all or part of their PS intake. At enrolment, weeks 1 and 4, caregivers completed a questionnaire on gastrointestinal symptoms, acceptability and ease of PS use. In study part 1, blood Tyr and Phe were assessed weekly; in part 2, weekly to fortnightly. In parts 1 and 2, weight and height were assessed at the study start and end. RESULTS: Nine of eleven children (82%), median age 15 years (range 8.6-17.7), took low Tyr/Phe CGMP PS over 28 days; it was continued for 12 months in n = 5 children. It was well accepted by 67% (n = 6/9), tolerated by 100% (n = 9/9) and improved gastrointestinal symptoms in 2 children. The median daily dose of protein equivalent from protein substitute was 60 g/day (range 45-60 g) with a median of 20 g/day (range 15 to 30 g) from natural protein. In part 2 (n = 5), a trend for improved blood Tyr was observed: 12 months pre-study, median Tyr was 490 µmol/L (range 200-600) and Phe 50 µmol/L (range 30-100); in the 12 months taking low Tyr/Phe CGMP PS, median Tyr was 430 µmol/L (range 270-940) and Phe 40 µmol/L (range 20-70). Normal height, weight and BMI z scores were maintained over 12 months. CONCLUSIONS: In HTI children, CGMP was well tolerated, with no deterioration in metabolic control or growth when studied over 12 months. The efficacy of CGMP in HTI needs further investigation to evaluate the longer-term impact on blood Phe concentrations and its potential influence on gut microflora.


Asunto(s)
Caseínas/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Tirosinemias/dietoterapia , Adolescente , Aminoácidos/administración & dosificación , Aminoácidos/sangre , Niño , Preescolar , Ciclohexanonas/administración & dosificación , Dieta/métodos , Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Femenino , Humanos , Masculino , Nitrobenzoatos/administración & dosificación , Fenilalanina/administración & dosificación , Fenilalanina/sangre , Estudios Prospectivos , Tirosina/administración & dosificación , Tirosina/sangre
2.
Nutrients ; 13(4)2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33923714

RESUMEN

Protein quality and quantity are important factors in determining lean body (muscle) mass (LBM). In phenylketonuria (PKU), protein substitutes provide most of the nitrogen, either as amino acids (AA) or glycomacropeptide with supplementary amino acids (CGMP-AA). Body composition and growth are important indicators of long-term health. In a 3-year prospective study comparing the impact of AA and CGMP-AA on body composition and growth in PKU, 48 children were recruited. N = 19 (median age 11.1 years, range 5-15 years) took AA only, n = 16 (median age 7.3 years, range 5-15 years) took a combination of CGMP-AA and AA, (CGMP50) and 13 children (median age 9.2 years, range 5-16 years) took CGMP-AA only (CGMP100). A dual energy X-ray absorptiometry (DXA) scan at enrolment and 36 months measured LBM, % body fat (%BF) and fat mass (FM). Height was measured at enrolment, 12, 24 and 36 months. No correlation or statistically significant differences (after adjusting for age, gender, puberty and phenylalanine blood concentrations) were found between the three groups for LBM, %BF, FM and height. The change in height z scores, (AA 0, CGMP50 +0.4 and CGMP100 +0.7) showed a trend that children in the CGMP100 group were taller, had improved LBM with decreased FM and % BF but this was not statistically significant. There appeared to be no advantage of CGMP-AA compared to AA on body composition after 3-years of follow-up. Although statistically significant differences were not reached, a trend towards improved body composition was observed with CGMP-AA when it provided the entire protein substitute requirement.


Asunto(s)
Aminoácidos/administración & dosificación , Composición Corporal/efectos de los fármacos , Caseínas/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Fenilcetonurias/fisiopatología , Absorciometría de Fotón , Adolescente , Estatura , Niño , Preescolar , Suplementos Dietéticos , Femenino , Crecimiento/efectos de los fármacos , Humanos , Estudios Longitudinales , Masculino , Fenilalanina/sangre , Fenilcetonurias/sangre , Fenilcetonurias/dietoterapia , Estudios Prospectivos , Resultado del Tratamiento
3.
Nutrients ; 13(2)2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33672234

RESUMEN

Aspartame is a phenylalanine containing sweetener, added to foods and drinks, which is avoided in phenylketonuria (PKU). However, the amount of phenylalanine provided by aspartame is unidentifiable from food and drinks labels. We performed a cross-sectional online survey aiming to examine the accidental aspartame consumption in PKU. 206 questionnaires (58% female) were completed. 55% of respondents (n = 114) were adults with PKU or their parent/carers and 45% (n = 92) were parents/carers of children with PKU. 74% (n = 152/206) had consumed food/drinks containing aspartame. Repeated accidental aspartame consumption was common and more frequent in children (p < 0.0001). The aspartame containing food/drinks accidentally consumed were fizzy drinks (68%, n = 103/152), fruit squash (40%, n = 61/152), chewing gum (30%, n = 46/152), flavoured water (25%, n = 38/152), ready to drink fruit squash cartons (23%, n = 35/152) and sports drinks (21%, n = 32/152). The main reasons described for accidental consumption, were manufacturers' changing recipes (81%, n = 123/152), inability to check the ingredients in pubs/restaurants/vending machines (59%, n = 89/152) or forgetting to check the label (32%, n = 49/152). 23% (n= 48/206) had been prescribed medicines containing aspartame and 75% (n = 36/48) said that medicines were not checked by medics when prescribed. 85% (n = 164/192) considered the sugar tax made accidental aspartame consumption more likely. Some of the difficulties for patients were aspartame identification in drinks consumed in restaurants, pubs, vending machines (77%, n = 158/206); similarities in appearance of aspartame and non-aspartame products (62%, n = 127/206); time consuming shopping/checking labels (56%, n = 115/206); and unclear labelling (55%, n = 114/206). These issues caused anxiety for the person with PKU (52%, n = 106/206), anxiety for parent/caregivers (46%, n = 95/206), guilt for parent/carers (42%, n = 87/206) and social isolation (42%, n = 87/206). It is important to understand the impact of aspartame and legislation such as the sugar tax on people with PKU. Policy makers and industry should ensure that the quality of life of people with rare conditions such as PKU is not compromised through their action.


Asunto(s)
Accidentes/estadística & datos numéricos , Aspartame/análisis , Alimentos/estadística & datos numéricos , Fenilalanina/análisis , Fenilcetonurias/dietoterapia , Adulto , Aspartame/efectos adversos , Niño , Estudios Transversales , Femenino , Alimentos/efectos adversos , Análisis de los Alimentos , Etiquetado de Alimentos , Humanos , Legislación Alimentaria , Masculino , Fenilalanina/efectos adversos , Restaurantes
4.
Nutrients ; 12(11)2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33182603

RESUMEN

A phenylalanine (protein)-restricted diet is the primary treatment for phenylketonuria (PKU). Patients are dependent on food protein labelling to successfully manage their condition. We evaluated the accuracy of protein labelling on packaged manufactured foods from supermarket websites for foods that may be eaten as part of a phenylalanine-restricted diet. Protein labelling information was evaluated for 462 food items ("free from", n = 159, regular, n = 303), divided into 16 food groups using supermarket website data. Data collection included protein content per portion/100 g when food was "as sold", "cooked" or "prepared"; cooking methods, and preparation instructions. Labelling errors affecting protein content were observed in every food group, with overall protein labelling unclear in 55% (n = 255/462) of foods. There was misleading, omitted, or erroneous (MOE) information in 43% (n = 68/159) of "free from" foods compared with 62% (n = 187/303) of regular foods, with fewer inaccuracies in "free from" food labelling (p = 0.007). Protein analysis was available for uncooked weight only but not cooked weight for 58% (n = 85/146) of foods; 4% (n = 17/462) had misleading protein content. There was a high rate of incomplete, misleading, or inaccurate data affecting the interpretation of the protein content of food items on supermarket websites. This could adversely affect metabolic control of patients with PKU and warrants serious consideration.


Asunto(s)
Dieta Sin Gluten/normas , Dieta con Restricción de Proteínas/normas , Proteínas en la Dieta/análisis , Etiquetado de Alimentos/normas , Fenilcetonurias/dietoterapia , Dieta Sin Gluten/métodos , Dieta con Restricción de Proteínas/métodos , Humanos , Fenilalanina/metabolismo , Reino Unido
5.
Nutrients ; 12(11)2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33137944

RESUMEN

BACKGROUND: Little is known about the optimal dietary treatment for citrin deficiency. Our aim is to describe the management of UK citrin deficiency patients. METHODS: A longitudinal retrospective review was performed. Data were collected from medical records on presenting signs and symptoms, dietary management and clinical outcome. RESULTS: data were collected on 32 patients from 21 families. 50% were females (16/32). Median age at diagnosis was 4 y (5 days-35 y) with 12 patients diagnosed in the neonatal period with neonatal intrahepatic cholestasis (NICCD), eight later in childhood (FTTDCD) and 12 by family screening based on index cases from five families. No patient had adult-onset type II citrullinemia. The patient age at the time of data collection was a median of 11 y (1-44 y). 91% (29/32) of patients had normal physical and neurological development, 47% (15/32) experienced recurrent unexplained abdominal pain and 9% (3/32) episodes of hypoglycaemia. Siblings had different phenotypes (5 families had > 1 affected patient). Most patients preferred high protein foods, limiting sugar-containing foods. Only 41% (13/32) were prescribed a low CHO, high protein, high fat diet (restriction varied) and two used medium chain triglyceride (MCT) supplements. No patient was prescribed drug therapy. Twenty-five per cent (8/32) of patients were underweight and 41% (13/32) had height <-1 z-scores. CONCLUSIONS: patients presented with various phenotypes, symptoms and suboptimal growth. Symptoms and biochemical markers improved with age, but height remained low in some. More research is necessary to assess the effectiveness of dietary approaches in improving clinical outcomes and symptoms in citrin deficiency.


Asunto(s)
Citrulinemia/dietoterapia , Dieta Alta en Grasa/métodos , Dieta Rica en Proteínas y Pobre en Hidratos de Carbono/métodos , Suplementos Dietéticos , Estado de Salud , Adolescente , Adulto , Biomarcadores/sangre , Niño , Preescolar , Citrulinemia/sangre , Citrulinemia/fisiopatología , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Fenotipo , Estudios Retrospectivos , Resultado del Tratamiento , Triglicéridos/administración & dosificación , Reino Unido , Adulto Joven
6.
Nutrients ; 12(8)2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32823853

RESUMEN

In Phenylketonuria (PKU), the peptide structure of the protein substitute (PS), casein glycomacropeptide (CGMP), is supplemented with amino acids (CGMP-AA). CGMP may slow the rate of amino acid (AA) absorption compared with traditional phenylalanine-free amino acids (Phe-free AA), which may improve nitrogen utilization, decrease urea production, and alter insulin response. AIM: In children with PKU, to compare pre and postprandial AA concentrations when taking one of three PS's: Phe-free AA, CGMP-AA 1 or 2. METHODS: 43 children (24 boys, 19 girls), median age 9 years (range 5-16 years) were studied; 11 took CGMP-AA1, 18 CGMP-AA2, and 14 Phe-free AA. Early morning fasting pre and 2 h postprandial blood samples were collected for quantitative AA on one occasion. A breakfast with allocated 20 g protein equivalent from PS was given post fasting blood sample. RESULTS: There was a significant increase in postprandial AA for all individual AAs with all three PS. Postprandial AA histidine (p < 0.001), leucine (p < 0.001), and tyrosine (p < 0.001) were higher in CGMP-AA2 than CGMP-AA1, and leucine (p < 0.001), threonine (p < 0.001), and tyrosine (p = 0.003) higher in GCMP-AA2 than Phe-free AA. This was reflective of the AA composition of the three different PS's. CONCLUSIONS: In PKU, the AA composition of CGMP-AA influences 2 h postprandial AA composition, suggesting that a PS derived from CGMP-AA may be absorbed similarly to Phe-free AA, but this requires further investigation.


Asunto(s)
Aminoácidos/administración & dosificación , Aminoácidos/metabolismo , Caseínas/administración & dosificación , Caseínas/metabolismo , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/metabolismo , Fenilalanina/efectos adversos , Fenilcetonurias/dietoterapia , Fenilcetonurias/metabolismo , Periodo Posprandial/fisiología , Adolescente , Factores de Edad , Aminoácidos/sangre , Niño , Preescolar , Femenino , Humanos , Insulina/metabolismo , Masculino , Nitrógeno/metabolismo , Fenilcetonurias/sangre , Factores de Tiempo , Urea/metabolismo
7.
Nutrients ; 12(8)2020 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-32722073

RESUMEN

In phenylketonuria (PKU), variable dietary advice provided by health professionals and social media leads to uncertainty for patients/caregivers reliant on accurate, evidence based dietary information. Over four years, 112 consensus statements concerning the allocation of foods in a low phenylalanine diet for PKU were developed by the British Inherited Metabolic Disease Dietitians Group (BIMDG-DG) from 34 PKU treatment centres, utilising 10 rounds of Delphi consultation to gain a majority (≥75%) decision. A mean of 29 UK dietitians (range: 18-40) and 18 treatment centres (range: 13-23) contributed in each round. Statements encompassed all foods/food groups divided into four categories based on defined protein/phenylalanine content: (1) foods high in protein/phenylalanine (best avoided); (2) foods allowed without restriction including fruit/vegetables containing phenylalanine ≤75 mg/100 g and most foods containing protein ≤0.5 g/100 g; (3) foods that should be calculated/weighed as an exchange food if they contain protein exchange ingredients (categorized into foods with a protein content of: >0.1 g/100 g (milk/plant milks only), >0.5 g/100 g (bread/pasta/cereal/flours), >1 g/100 g (cook-in/table-top sauces/dressings), >1.5 g/100 g (soya sauces)); and (4) fruit/vegetables containing phenylalanine >75 mg/100 g allocated as part of the protein/phenylalanine exchange system. These statements have been endorsed and translated into practical dietary management advice by the medical advisory dietitians for the National Society for PKU (NSPKU).


Asunto(s)
Dieta con Restricción de Proteínas/normas , Proteínas en la Dieta/análisis , Dietética/normas , Fenilalanina/análisis , Fenilcetonurias/dietoterapia , Consenso , Técnica Delphi , Dieta con Restricción de Proteínas/métodos , Etiquetado de Alimentos/normas , Humanos , Reino Unido
8.
Nutrients ; 12(6)2020 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-32630585

RESUMEN

Special low protein foods (SLPFs) are essential in a low phenylalanine diet for treating phenylketonuria (PKU). With little known about their nutritional composition, all SLPFs on UK prescription were studied (n = 146) and compared to equivalent protein-containing foods (n = 190). SLPF nutritional analysis was obtained from suppliers/manufacturers. Comparable information about regular protein-containing foods was obtained from online UK supermarkets. Similar foods were grouped together, with mean nutritional values calculated for each subgroup (n = 40) and percentage differences determined between SLPFs and regular food subgroups. All SLPF subgroups contained 43-100% less protein than regular foods. Sixty-three percent (n = 25/40) of SLPF subgroups contained less total fat with palm oil (25%, n = 36/146) and hydrogenated vegetable oil (23%, n = 33/146) key fat sources. Sixty-eight percent (n = 27/40) of SLPF subgroups contained more carbohydrate, with 72% (n = 105/146) containing added sugar. Key SLPF starch sources were maize/corn (72%; n = 105/146). Seventy-seven percent (n = 113/146) of SLPFs versus 18% (n = 34/190) of regular foods contained added fibre, predominantly hydrocolloids. Nine percent of SLPFs contained phenylalanine > 25 mg/100 g and sources of phenylalanine/protein in their ingredient lists. Stricter nutritional composition regulations for SLPFs are required, identifying maximum upper limits for macronutrients and phenylalanine, and fat and carbohydrate sources that are associated with healthy outcomes.


Asunto(s)
Proteínas en la Dieta/análisis , Alimentos Formulados/análisis , Nutrientes/análisis , Valor Nutritivo , Fenilalanina/análisis , Fenilcetonurias/dietoterapia , Grasas de la Dieta/análisis , Etiquetado de Alimentos , Humanos , Legislación Alimentaria , Reino Unido
9.
Nutrients ; 12(4)2020 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-32325917

RESUMEN

In a longitudinal retrospective study, we aimed to assess natural protein (NP) tolerance and metabolic control in a cohort of 20 Hereditary Tyrosinaemia type I (HTI) patients. Their median age was 12 years ([3.2-17.7 years], n = 11 female, n = 8 Caucasian, n = 8 Asian origin, n = 2 Arabic and n = 2 Indian). All were on nitisinone (NTBC) with a median dose of 0.7 g/kg/day (range 0.4-1.5 g/kg/day) and were prescribed a tyrosine (Tyr)/phenylalanine (Phe)-restricted diet supplemented with Tyr/Phe-free L-amino acids. Data were collected on clinical signs at presentation, medical history, annual dietary prescriptions, and blood Phe and Tyr levels from diagnosis until transition to the adult service (aged 16-18 years) or liver transplantation (if it preceded transition). The median age of diagnosis was 2 months (range: 0 to 24 months), with n = 1 diagnosed by newborn screening, n = 3 following phenylketonuria (PKU) screening and n = 7 by sibling screening. Five patients were transplanted (median age 6.3 years), and one died due to liver cancer. The median follow-up was 10 years (3-16 years), and daily prescribed NP intake increased from a median of 5 to 24 g/day. Lifetime median blood Tyr (370 µmol/L, range 280-420 µmol/L) and Phe (50 µmol/L, 45-70 µmol/L) were maintained within the target recommended ranges. This cohort of HTI patients were able to increase the daily NP intake with age while maintaining good metabolic control. Extra NP may improve lifelong adherence to the diet.


Asunto(s)
Aminoácidos Neutros/administración & dosificación , Fenómenos Fisiológicos Nutricionales Infantiles/fisiología , Ciclohexanonas/administración & dosificación , Suplementos Dietéticos , Nitrobenzoatos/administración & dosificación , Tirosinemias/dietoterapia , Tirosinemias/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Cooperación del Paciente , Fenilalanina/sangre , Estudios Retrospectivos , Tirosina/sangre , Tirosinemias/sangre , Tirosinemias/genética
11.
J Breath Res ; 14(1): 016001, 2019 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-31476741

RESUMEN

In clinical practice, caregivers of children with phenylketonuria (PKU) report that their children have breath malodour. This might be linked to the regular consumption of low phenylalanine (Phe)/Phe-free protein substitutes (PS), which are an essential component of a low-Phe diet. Oral malodour can negatively affect interpersonal communication, lead to bullying, low self-esteem and social isolation. In this longitudinal cross-over study, exhaled volatile organic compounds (VOCs) were measured using gas chromatography-ion mobility spectrometry. 40 children (20 PKU, 20 controls) were recruited. Subjects with PKU took either L-Amino Acid (L-AA) or Casein Glycomacropeptide (CGMP-AA) exclusively for 1 week, in a randomised order. On the seventh day, seven exhaled breath samples were collected over a 10 h period. Subjects then transferred to the other PS for a week and on day seven, provided seven further breath samples. All subjects had a standardised menu using low-Phe food alternatives and all food intake was measured and recorded. In the PKU group, the aim was to collect samples 30 min after consuming PS. In 3 subjects, breath was collected 5 min post-PS consumption. Fasted L-AA and CGMP-AA breath samples contained a similar number of VOC peaks (10-12) as controls. Longitudinal breath testing results demonstrate that there was no significant difference in the number of exhaled VOCs, comparing L-AA or CGMP-AA with controls, or between PS (12-18 VOC peaks). Breath analysed immediately after consumption of PS (n = 3) showed an immediate increase in the number of VOC peaks (25-30), but these were no longer detectable at 30 min post-consumption. This suggests PS have a transient effect on exhaled breath. Measurements taken 30 min after consuming L-AA or CGMP-AA were not significantly different to controls. This indicates that timing food and drinks with PS consumption may be a potential solution for carers to reduce or eliminate unpleasant PS-related breath odours.


Asunto(s)
Caseínas/uso terapéutico , Suplementos Dietéticos , Fragmentos de Péptidos/uso terapéutico , Fenilalanina/uso terapéutico , Fenilcetonurias/diagnóstico , Adolescente , Pruebas Respiratorias , Niño , Factores de Confusión Epidemiológicos , Estudios Cruzados , Espiración , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Estudios Longitudinales , Masculino , Encuestas y Cuestionarios , Compuestos Orgánicos Volátiles/análisis
12.
Nutrients ; 11(3)2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30823411

RESUMEN

Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. Methods: This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Phe-free l-amino acids (l-AA) assessing blood Phe and tyrosine (Tyr) variability over 24 h in 19 children (7 boys) with PKU, with a median age of 10 years (6⁻16). Subjects were randomised to 3 dietary regimens: (1) R1, CGMP-AA and usual dietary Phe (CGMP + Phe); (2) R2, CGMP-AA - Phe content of CGMP-AA from usual diet (CGMP - Phe); and (3) R3, l-AA and usual dietary Phe. Each regimen was administered for 14 days. Over the last 48 h on days 13 and 14, blood spots were collected every 4 h at 08 h, 12 h, 16 h, 20 h, 24 h, and 04 h. Isocaloric intake and the same meal plan and protein substitute dosage at standardised times were maintained when blood spots were collected. Results: Eighteen children completed the study. Median Phe concentrations over 24 h for each group were (range) R1, 290 (30⁻580), R2, 220 (10⁻670), R3, 165 (10⁻640) µmol/L. R1 vs. R2 and R1 vs. R3 p < 0.0001; R2 vs. R3 p = 0.0009. There was a significant difference in median Phe at each time point between R1 vs. R2, p = 0.0027 and R1 vs. R3, p < 0.0001, but not between any time points for R2 vs. R3. Tyr was significantly higher in both R1 and R2 [70 (20⁻240 µmol/L] compared to R3 [60 (10⁻200) µmol/L]. In children < 12 years, blood Phe remained in the target range (120⁻360 µmol/L), over 24 h, for 75% of the time in R1, 72% in R2 and 64% in R3; for children aged ≥ 12 years, blood Phe was in target range (120⁻600 µmol/L) in R1 and R2 for 100% of the time, but 64% in R3. Conclusions: The residual Phe in CGMP-AA increased blood Phe concentration in children. CGMP-AA appears to give less blood Phe variability compared to l-AA, but this effect may be masked by the increased blood Phe concentrations associated with its Phe contribution. Reducing dietary Phe intake to compensate for CGMP-AA Phe content may help.


Asunto(s)
Caseínas/administración & dosificación , Caseínas/farmacología , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/farmacología , Fenilalanina/sangre , Tirosina/sangre , Niño , Suplementos Dietéticos , Femenino , Humanos , Masculino , Fenilalanina/metabolismo , Fenilcetonurias , Tirosina/metabolismo
13.
Nutrients ; 11(3)2019 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-30841589

RESUMEN

Growth issues have been observed in young children with phenylketonuria (PKU), but studies are conflicting. In infancy, there is an increasing trend to introduce a second-stage semi-solid weaning protein substitute (WPS) but there is concern that this may not meet energy requirements. In this longitudinal, prospective study, 20 children with PKU transitioning to a WPS, and 20 non-PKU controls were observed monthly from weaning commencement (4⁻6 months) to 12 m and at 15, 18 and 24 months of age for: weight, length, head circumference, body mass index (BMI), energy and macronutrient intake. Growth parameters were within normal range at all ages in both groups with no significant difference in mean z-scores except for accelerated length in the PKU group. No child with PKU had z-scores < -2 for any growth parameter at age 2 years. Total protein and energy intake in both groups were similar at all ages; however, from 12⁻24 months in the PKU group, the percentage of energy intake from carbohydrate increased (60%) but from fat decreased (25%) and inversely for controls (48% and 36%). In PKU, use of low volume WPS meets Phe-free protein requirements, facilitates transition to solid foods and supports normal growth. Further longitudinal study of growth, body composition and energy/nutrient intakes in early childhood are required to identify any changing trends.


Asunto(s)
Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Fenilcetonurias/dietoterapia , Fenilcetonurias/fisiopatología , Destete , Estatura/fisiología , Peso Corporal/fisiología , Estudios de Casos y Controles , Cefalometría , Preescolar , Ingestión de Energía , Femenino , Cabeza , Humanos , Lactante , Estudios Longitudinales , Masculino , Nutrientes/análisis , Estudios Prospectivos
14.
Orphanet J Rare Dis ; 14(1): 2, 2019 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-30606267

RESUMEN

BACKGROUND: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients. METHODOLOGY: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added. RESULTS: The statements incorporated controversial dietary topics including: a practical 'scale' for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU. CONCLUSIONS: The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.


Asunto(s)
Etiquetado de Alimentos/métodos , Fenilalanina/metabolismo , Fenilcetonurias/dietoterapia , Consenso , Técnica Delphi , Humanos , Fenilalanina/química , Encuestas y Cuestionarios
15.
Ann Nutr Metab ; 65(1): 42-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25196394

RESUMEN

BACKGROUND: In phenylketonuria (PKU), phenylalanine-free L-amino acid supplements are the major source of dietary micronutrients. METHODS: Four hundred fifty-two retrospective annual/bi-annual non-fasting blood samples for nutritional markers (plasma zinc, selenium, and serum folate) from 78 subjects aged 1-16 years (median number of blood samples: 6, range 1-14) were analysed over 12 years. Longitudinal blood result data were available for 51 subjects (65%). The dietary intake from supplements was calculated. RESULTS: The median intakes of all of the micronutrients studied were >200% of the reference nutrient intakes (RNI). There was no statistical correlation between dietary intake and nutritional markers outside of the normal reference range (RR) except for selenium, but there was a correlation between a lower plasma zinc, plasma selenium and haemoglobin status and better blood phenylalanine control in 1- to 4-year-old children. On at least one occasion, the individual plasma concentrations of zinc (71%, n = 54/76) and selenium (21%, n = 16/75) were below the RR; however, the concentrations of selenium (41%, n = 31/75) and serum folate (83%, n = 34/41) were also above the RR. Dietary intakes exceeded the upper tolerable intakes for zinc and copper (32%, n = 25) and folate (65%, n = 51). Individual longitudinal data demonstrated little change in micronutrient status over time. CONCLUSIONS: In PKU, biochemical micronutrient deficiencies are common despite micronutrient intakes above the RNI. Further study of the nutritional profiling of L-amino acid supplements in PKU is needed.


Asunto(s)
Micronutrientes/administración & dosificación , Micronutrientes/deficiencia , Estado Nutricional , Fenilcetonurias/dietoterapia , Adolescente , Aminoácidos/administración & dosificación , Biomarcadores/sangre , Niño , Preescolar , Cobre/sangre , Dieta , Suplementos Dietéticos , Femenino , Ácido Fólico/sangre , Humanos , Lactante , Estudios Longitudinales , Masculino , Micronutrientes/sangre , Fenilalanina/sangre , Fenilcetonurias/sangre , Estudios Retrospectivos , Selenio/sangre , Zinc/sangre
16.
Int J Hyperthermia ; 29(5): 464-73, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23862980

RESUMEN

Cancer immunotherapy aims to generate long-lived, tumour-specific adaptive immunity to limit dysregulated tumour progression and metastasis. Tumour vasculature has emerged as a critical checkpoint controlling the efficacy of immunotherapy since it is the main access point for cytotoxic T cells to reach tumour cell targets. Therapeutic success has been particularly challenging to achieve because of the local, cytokine-rich inflammatory milieu that drives a pro-tumourigenic programme supporting the growth and survival of malignant cells. Here, we focus on recent evidence that systemic thermal therapy can switch the activities of the inflammatory cytokine, interleukin-6 (IL-6), to a predominantly anti-tumourigenic function that promotes anti-tumour immunity by mobilising T cell trafficking in the recalcitrant tumour microenvironment.


Asunto(s)
Hipertermia Inducida , Interleucina-6/inmunología , Neoplasias/terapia , Animales , Linfocitos T CD8-positivos/inmunología , Humanos , Inmunoterapia Adoptiva , Neoplasias/inmunología , Microambiente Tumoral/inmunología
17.
Cancer Immunol Res ; 1(4): 210-6, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24490177

RESUMEN

A major goal of cancer immunology is to stimulate the generation of long-lasting, tumor antigen-specific immune responses that recognize and destroy tumor cells. This article discusses advances in thermal medicine with the potential to improve cancer immunotherapy. Accumulating evidence indicates that survival benefits are accorded to individuals who achieve an increase in body temperature (i.e. fever) following infection. Furthermore, accumulating evidence indicates that physiological responses to hyperthermia impact the tumor microenvironment through temperature-sensitive check-points that regulate tumor vascular perfusion, lymphocyte trafficking, inflammatory cytokine expression, tumor metabolism, and innate and adaptive immune function. Nevertheless, the influence of thermal stimuli on the immune system, particularly the antitum or immune response, remains incompletely understood. In fact, temperature is still rarely considered as a critical variable in experimental immunology. We suggest that more attention should be directed to the role of temperature in the regulation of the immune response and that thermal therapy should be tested in conjunction with immunotherapy as a multi-functional adjuvant that modulates the dynamics of the tumor microenvironment.


Asunto(s)
Fiebre/inmunología , Sistema Inmunológico/fisiología , Neoplasias/inmunología , Temperatura , Animales , Hipoxia de la Célula , Citocinas/inmunología , Humanos , Hipertermia Inducida , Inmunoterapia , Ratones , Microambiente Tumoral
18.
Mol Genet Metab ; 104 Suppl: S64-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21978770

RESUMEN

BACKGROUND: In children with phenylketonuria (PKU), it is possible that high carbohydrate protein substitutes may adversely affect blood phenylalanine control. We evaluated if a low carbohydrate, 'ready-to-drink' protein substitute would impact on short term blood phenylalanine control, weight and appetite in children with PKU aged 3-10 years. METHODS: This was a 3-part, 5-week randomised, controlled, crossover study in which two different carbohydrate/protein-equivalent ratios in protein substitute [control protein substitute (CPS) median 1:1; trial protein substitute (TPS) 0.5:1] were compared. The effects on feeding behaviour, weight change and phenylalanine concentrations were studied. Fourteen children (12 boys; median age 6.3 y, range 3 to 9.7 y) with PKU on diet were recruited from 2 treatment centres. RESULTS: Phenylalanine control did not deteriorate with TPS and remained unchanged between pre-study and CPS (p = 0.783). No statistical differences were noted in energy intake between the two study parts. Any changes in weight were similar between the two groups and there was limited change in feeding behaviour. CONCLUSION: This study suggests that the carbohydrate/protein-equivalent ratio of protein substitutes can be reduced to 0.5:1 with no loss of blood phenylalanine control or adverse effect on weight gain in children with PKU.


Asunto(s)
Apetito/fisiología , Carbohidratos de la Dieta/uso terapéutico , Proteínas en la Dieta/uso terapéutico , Crecimiento y Desarrollo , Fenilalanina/sangre , Fenilcetonurias/sangre , Fenilcetonurias/dietoterapia , Adolescente , Antropometría , Peso Corporal , Niño , Preescolar , Suplementos Dietéticos , Conducta Alimentaria , Femenino , Humanos , Masculino , Fenilcetonurias/fisiopatología
19.
J Clin Invest ; 121(10): 3846-59, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21926464

RESUMEN

Immune cells are key regulators of neoplastic progression, which is often mediated through their release of cytokines. Inflammatory cytokines such as IL-6 exert tumor-promoting activities by driving growth and survival of neoplastic cells. However, whether these cytokines also have a role in recruiting mediators of adaptive anticancer immunity has not been investigated. Here, we report that homeostatic trafficking of tumor-reactive CD8+ T cells across microvascular checkpoints is limited in tumors despite the presence of inflammatory cytokines. Intravital imaging in tumor-bearing mice revealed that systemic thermal therapy (core temperature elevated to 39.5°C ± 0.5°C for 6 hours) activated an IL-6 trans-signaling program in the tumor blood vessels that modified the vasculature such that it could support enhanced trafficking of CD8+ effector/memory T cells (Tems) into tumors. A concomitant decrease in tumor infiltration by Tregs during systemic thermal therapy resulted in substantial enhancement of Tem/Treg ratios. Mechanistically, IL-6 produced by nonhematopoietic stromal cells acted cooperatively with soluble IL-6 receptor-α and thermally induced gp130 to promote E/P-selectin- and ICAM-1-dependent extravasation of cytotoxic T cells in tumors. Parallel increases in vascular adhesion were induced by IL-6/soluble IL-6 receptor-α fusion protein in mouse tumors and patient tumor explants. Finally, a causal link was established between IL-6-dependent licensing of tumor vessels for Tem trafficking and apoptosis of tumor targets. These findings suggest that the unique IL-6-rich tumor microenvironment can be exploited to create a therapeutic window to boost T cell-mediated antitumor immunity and immunotherapy.


Asunto(s)
Interleucina-6/metabolismo , Neoplasias/irrigación sanguínea , Neoplasias/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular/inmunología , Selectina E/metabolismo , Humanos , Hipertermia Inducida , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones , Microvasos/inmunología , Modelos Inmunológicos , Neoplasias/patología , Neoplasias/terapia , Selectina-P/metabolismo , Transducción de Señal , Microambiente Tumoral/inmunología
20.
Cancer Res ; 71(11): 3872-80, 2011 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-21512134

RESUMEN

Human and rodent solid tumors often exhibit elevated interstitial fluid pressure (IFP). This condition is recognized as a prognostic indicator for reduced responses to therapy and decreased disease-free survival rate. In the present study, we tested whether induction of a thermoregulatory-mediated increase in tissue blood flow, induced by exposure of mice to mild environmental heat stress, could influence IFP and other vascular parameters within tumors. Using several murine tumor models, we found that heating results in a sustained reduction in tumor IFP correlating with increased tumor vascular perfusion (measured by fluorescent imaging of perfused vessels, laser Doppler flowmetry, and MRI) as well as a sustained reduction in tumor hypoxia. Furthermore, when radiation therapy was administered 24 hours postheating, we observed a significant improvement in efficacy that may be a result of the sustained reduction in tumor hypoxia. These data suggest, for the first time, that environmental manipulation of normal vasomotor function is capable of achieving therapeutically beneficial changes in IFP and microvascular function in the tumor microenvironment.


Asunto(s)
Neoplasias del Colon/terapia , Hipertermia Inducida/métodos , Neoplasias Mamarias Experimentales/terapia , Melanoma Experimental/terapia , Animales , Temperatura Corporal/fisiología , Hipoxia de la Célula/fisiología , Neoplasias del Colon/irrigación sanguínea , Neoplasias del Colon/radioterapia , Terapia Combinada , Modelos Animales de Enfermedad , Líquido Extracelular/fisiología , Femenino , Humanos , Neoplasias Mamarias Experimentales/irrigación sanguínea , Neoplasias Mamarias Experimentales/radioterapia , Melanoma Experimental/irrigación sanguínea , Melanoma Experimental/radioterapia , Ratones , Ratones Endogámicos BALB C
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