Sphere research summary

Impact Of The Amino Acid Profile Of Casein Glycomacropeptide On Metabolic Control In Children With PKU.

Daly A, Chahal S, Evans S, MacDonald A.

In PKU, casein glycomacropeptide is supplemented with additional L-amino acids (CGMP-AA). The effect of the added L-amino acid ratio on metabolic control is unknown. The longitudinal changes in blood phenylalanine (Phe) and tyrosine (Tyr) in CGMP-AA over 15 months were examined in a prospective controlled trial in PKU children where the added amino acid element of CGMP-AA was modified in three different ways. The results were compared to a parallel control group that only took traditional L-amino acids supplements (L-AA).

21 children with a median age of 11 years (6–16 years) were recruited, with 12 on CGMP-AA and 9 on L-AA as their protein substitute (PS) source. Three CGMP-AA products were trialled: CGMP–AA1 (amino acid profile matched WHO 2007 amino acid requirements) was used for 6 months, CGMP–AA2 (extra tyrosine) for 4 months, and CGMP–AA3 (extra-large neutral amino acids) for 5 months. Phe and Tyr blood spots were collected on a weekly basis. The results for the study and control groups were compared to the results for the 12 months preceding study entry. The CGMP-AA products contained 30 mg Phe/20 g protein equivalent.

The median total PS provided by CGMP-AA1 was 50% and provided 45mg/Phe per day. CGMP-AA2 provided 50% median total PS and 45mg/Phe per day and CGMP-AA3 provided 75% median total PS and 68mg/Phe per day. Median blood Phe increased with CGMP-AA1 (p = 0.009) whereas median blood Phe remained unchanged for both CGMP-AA2 and CGMP-AA3 when compared to pre-study levels (Phe [μmol] pre-study, 275; CGMP-AA1, 378, CGMP2-AA2, 268; CGMPAA3, 290). A significant improvement in median tyrosine results was observed in the CGMP-AA 3 group (p = 0.03) when compared to pre-study levels (Tyr [μmol] pre-study, 50; CGMP-AA1, 45, CGMP2-AA2, 50; CGMP-AA3, 60). Median Tyr did not change throughout the study for the control group.

Metabolic control in PKU children is significantly impacted by the amino acid profile of added L-amino acids in CGMP-AA.

Journal of Inherited Metabolic Disease Reports 39 (Suppl. 1): S85. P-099

Glycomacropeptide In Children With Phenylketonuria: Does Its Phenylalanine Content Affect Blood Phenylalanine Control?

Daly A, Evans S, Chahal S, Santra S and MacDonald A

Individuals with phenylketonuria (PKU) require dietary management which include protein substitutes. Protein substitutes have traditionally been phenylalanine-free and based on L-amino acids (Phe-free LAA). An alternative is casein glycomacropeptide (CGMP) which contains a residual amount of phenylalanine. The aim of this study was to monitor the impact of CGMP-amino acid (CGMP-AA) protein substitute on blood phenylalanine control.

A prospective pilot study was carried out, for 6 months, on 22 children with PKU. Patients were given either CGMP-AA or Phe-free LAA based on individual preference. Patients given Phe-free LAA received their usual L-AA protein substitute throughout the study. Patients in the CGMP-AA group were either partially or wholly transitioned from Phe-free LAA, dependent on blood phenylalanine concentration. The proportion of CGMP-AA provided was titrated to maintain phenylalanine in the target range. Outcome measures included the measurement of phenylalanine, tyrosine, and Phe:Tyr ratio and were compared with each patient’s own blood results from the previous year.

Median age was 11 years (range 6-16 years). Twelve patients received CGMP-AA, nine Phe-free L-AA; one patient was withdrawn from the CGMP-AA group. Within the CGMP-AA group there was a significant increase in blood phenylalanine (317 μmol/L vs 275 μmol/L; p=0.02), decrease in tyrosine (40 μmol/L vs 50 μmol/L; p=0.03) and an increase in Phe:Tyr ratio (8:1 vs 4.9:1; p=0.02). No significant differences in phenylalanine concentrations, tyrosine or Phe:Tyr ratios (p=0.9) between the two groups were observed. Acceptance of the CGMP-AA was higher with the children compared with the Phe-free LAA.

Children taking CGMP-AA maintained blood phenylalanine concentrations within the target range, however there was a deterioration in blood phenylalanine control. CGMP requires careful monitoring when used in the dietary management of children with PKU.

J Hum Nutr Diet. 2017 Aug;30(4):515-523

Nutritional Status In Children With PKU: Glycomacropeptide Compared With Phenylalanine Free-AA

Daly A, Evans S, Chahal S, Santra S, Pinto A, Rocha J, van Spronsen SJ and MacDonald A

Individuals with phenylketonuria (PKU) require dietary management which includes protein substitutes. These have traditionally been phenylalanine-free and based on L-amino acids (Phe-free LAA). An alternative is casein glycomacropeptide (CGMP). The aim of this study was to monitor the impact of CGMP-amino acid (CGMP-AA) protein substitutes on micronutrient status in children with PKU.

48 children (29 on CGMPAA2 19 on L-AA) all started with 100% L-AA protein substitute at baseline. In the CGMP-AA group subjects partially or wholly replaced Phe-free L-AA with CGMP-AA, replacement was gradual and titrated the blood phe levels. L-AA group consumed 100% L-AA protein substitutes. Micronutrient status was evaluated at baseline and 6 months after introducing cGMP-AA. Samples were tested for zinc, selenium, C-reactive protein, haemoglobin, cell volume, ferritin, vitamin B12 and 25-hydroxy vitamin D.

At 6 months cGMP-AA group participants consumed a median of 75% protein substitute intake as CGMP, with 25% from L-AA. Compared to the L-AA group, there was a significant increase in selenium concentration between baseline and 6-months in both whole blood and plasma (p=0.0002, p=0.0007) in the CGMP group . In patients treated with CGMP, but not L-AA, ferritin decreased between baseline and 6-months (p=0.0006) although median values remained within the recommended range. All other nutritional markers assessed were within the normal range at 6-months, except for vitamin B12 which had a concentration above the recommended range in both groups.

Both protein substitutes were successful in maintaining nutritional blood markers within the reference range. An increase in plasma and whole blood selenium was observed in the CGMP group which may indicate superior antioxidant properties of the product.

J Inherit Metab Dis (2018) 41(Suppl 1): 1.

Variability Of Phenylalanine Concentrations Over 24 Hours Using Two Different Protein Substitutes And Changing Dietary Phenylalanine Intake

Daly A, Evans S, Chahal S, Santra S, Pinto A, Gingell C, Rocha J, van Spronsen FJ, Jackson R and MacDonald A

Individuals with phenylketonuria (PKU) require dietary management including a proteinsubstitute. Studies have suggested that blood phenylalanine (Phe) variability may be stabilised through the use of glycomacropeptide (CGMP). The aim of this study was to assess blood Phe variability over 24 hours in patients receiving either CGMP or Phe-free L-amino acid (LAA).

A 3-arm, randomised, controlled, cross-over study was carried out in 18 children with PKU. Isocaloric intake was maintained. The dietary regimen on each arm was followed by each participant for 14 days: 1. CGMP-AA only (no dietary Phe adjustment), 2. CGMP-AA2 (Phe content of GMP removed from dietary Phe allowance), 3. Phe-free LAA (no dietary Phe adjustment). On days 13 and 14, blood samples were collected every 4 hours for 48 hours and analysed for Phe concentrations.

The median Phe concentrations over 24 hours were statistically significant between each arm of the study (see Table). CGMP without dietary Phe adjustment does lead to higher blood phenylalanine concentrations in children with PKU, however blood concentrations remained within the target treatment range. No significant difference in the rate of change of Phe levels over the 24-hour period was observed between groups.

These findings indicate that reducing the dietary phe to compensate for phe contained in CGMP-AA enables a more consistent blood phe profile, although the difference in the rate of change did not reach statistical significance.

Median Phenylalanine concentrations of 4 hourly bloodspots over 24 hours.

J Inherit Metab Dis (2018) 41(Suppl 1): 1

Prospective Study: Glycomacropeptide And Conventional Amino Acid Protein Substitute In Children. Effect On Blood Phenylalanine And Growth

Daly A, Evans S, Chahal S, Santra S, Pinto A, Hogler W, Gingell C, Richa J, van Spronsen FJ and MacDonald A

Individuals with phenylketonuria (PKU) require dietary management which includes proteinsubstitutes. These have traditionally been phenylalanine-free and based on L-amino acids (Phe-free LAA). An alternative is casein glycomacropeptide (CGMP) which contains a residual amount of phenylalanine. CGMP has been reported to potentially provide additional health benefits. The aim of this study was to monitor the impact of CGMP-PS on blood Phe, Tyr, Phe:Tyr ratio, weight, height and BMI z scores.

48 children (29 on CGMPAA2 19 on L-AA) all started with 100% L-AA protein substitute at baseline. In the CGMP-AA group subjects partially or wholly replaced Phe-free L-AA with CGMP-AA, replacement was gradual and titrated the blood phe levels. L-AA group consumed 100% L-AA protein substitutes. Micronutrient status was evaluated at baseline and 6 months after introducing cGMP-AA. Nutritional and anthropometric parameters were measured at baseline, 6 and 12-months.

At the end of 12 months 48% of subjects were able to completely replace their L-AA PS with cGMP-AA as their single source of PS. In the CGMP group cGMP-AA provided a median 75% (30-100%) of the total protein substitute intake with the remaining 25% from L-AA. There was no difference between cGMP and L-AA for blood phe, tyr or anthropometry. In cGMP group there was a significant increase of phe between baseline and 6 months (p=0.06) and baseline and 12 months (p<0.001). Baseline average Phe: 270µmol/L (170-430), 6m average Phe: 300µmol/L (124-485), 12m average Phe: 300µmol/L (200-490). Patients in the CGMP group, but not in the control group increased in weight (p=0.0001) and BMI (p=0.0001) between baseline and 12 months.

A significant rise in blood Phe (within the target treatment range) was observed in children managed with CGMP. CGMP can be used in the management of PKU children with careful introduction and monitoring but may only partially contribute to their protein substitute requirement.

J Inherit Metab Dis (2018) 41(Suppl 1): 1

The Effect Of Glycomacropeptide Versus Amino Acids On Phenylalanine And Tyrosine Variability Over 24 Hours In Children With PKU: A Randomized Controlled Trial

Daly A, Evans S, Chahal S, Santra S, Pinto A, Gingell C, Rocha J, Spronsen F, Jackson R, MacDonald A

Studies suggest that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is related with better protein utilization and less blood Phe variability. The objective of this study was to assess the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU.

This was a 6-week randomized controlled cross-over study that included 19 children with PKU, with a median age of 10 years old. They were randomized to 3 different dietary regimens for 14 days: R1 (CGMP-AA only as their protein substitute and usual dietary Phe), R2 (CGMPAA only but the amount of Phe contained in the CGMP-AA was deducted from usual diet) and R3 (children took Phe-free L-AA with their usual dietary Phe allowance). Over the last 48 h on days 13 and 14, blood spots were collected every 4 hours.

Eighteen children completed the study.

There was a significant difference in median Phe at each time point between R1 vs. R2 and R1 vs. R3, but not for R2 vs. R3. Blood Phe remained in the target range (120-360 mol/L) over 24h in children < 12 years, for 75% of the time in R1, 72% in R2 and 64% in R3. Older children had their blood Phe in the target range in R1 and R2 for 100% of the time, but 64% in R3. Tyrosine levels were significantly higher in both the CGMP groups compared the AA group.

Blood Phe concentration was increased by residual Phe in CGMP-AA. There may be less blood Phe variability with CGMP-AA when compared to L-AA, but this effect may be masked by the increased blood Phe concentrations. Reducing dietary Phe intake may help compensate for CGMP-AA Phe content.

Nutrients. 2019 Feb 28;11(3).

Body Composition And Bone Mineral Density In PKU Children-Interim Results From A 3 Year Study

Daly A, Pinto A, Evans S, Rocha J C, Jackson R, MacDonald A

Diets severely restrictive in natural protein are a necessity in classical phenylketonuria (PKU), however may impair normal growth and bone mineralization. Protein substitutes provide amino acids, vitamins and minerals to help promote growth and bone development. The aim of this study was to compare the effects of the bioactive peptide glycomacropeptide (CGMP-AA) and synthetic amino acids (L-AA) on growth, body composition and bone mineral density (BMD) in children with PKU.

This 3-year study included 28 children: 18 on CGMP-AA (9 boys) and 10 on L-AA (7 boys). Median age at the end of the study was 11.2 y (range 8-19) for CGMP-AA and 15.9 y (range 9-18) for L-AA. Baseline measurements were taken as part of the BEX assessment, when allparticipants were on L-AA, they included weight (kg), height (cm), body mass index (kg/m2),fat free mass (g), % total fat, lean mass (LM), bone mineral content (g), BMD (g/cm2), bonemineral apparent density (g/cm2) and total body less head (g/cm2). These measures werealso registered at 36 months.

There were no significant differences between treatment group scores 36 months, however, fat-free mass was greater in the CGMP-AA than in for L-AA group at the end of the 36 months (p=0.01). Between genders, changes were observed in body mass index and bone mineral apparent density. At the end of the study, 7 children in the CGMP-AA group and 1 in the L-AA group were prepubertal.

The fact that some children were already on a prepubertal status may reflect the difference in fat free mass between groups. This study comes to no advantage of using CGMP-AA compared to L-AA in enhancing bone formation and measurements are relative to normal population standards. Further data is required.

Congress Abstract: Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM): Nutrients P-117

Investigation Of Paediatric PKU Breath Malodour, Comparing Glycomacropeptide With Phenylalanine Free L-Amino Acid Supplements

Tiele A, Daly A, Hattersley J, Pinto A, Evans S, Ashmore C, MacDonald A, Covington JA

Phenylketonuria (PKU) is an inherited metabolic disorder that causes Phe levels to accumulate in blood, potentially causing severe and irreversible neurological impairments. Effective management of the condition is achieved through dietary restriction of Phe and supplementation with Phe-free protein substitutes (PS). Patients and caregivers often associate intake of PS with bad breath and this can result in psychological distress, interfere with social interactions, lower self-esteem and body-image. Breath malodor in PKU has received little clinical or research attention, and it is unknown if this is an issue more common in PKU than a healthy population. This study focuses on two types of PS; Phe-free L-amino acids (L-AA) and low-Phe casein glycomacropeptide (CGMP-AA) to determine if there is any difference in breath malodour.

40 children (20 PKU, 20 controls) were recruited. PKU individuals with good adherence to diet were recruited. All participants completed a questionnaire at baseline and consumed the same diet throughout the study period. Intake was recorded via food diaries. Subjects with PKU took all their PS requirement from either L-AA or CGMP-AA exclusively for 7 days, in a randomised order. Each participant with PKU then switched to consuming the other PS for a 7-day period. On the 7th day of each week taking L-AA or CGMP-AA, 7 breath samples were collected over a 10 h period. In the PKU group, the aim was to collect samples 30 min after consuming the PS to allow subjects to digest and metabolize their meals and PS. Breath malodour was measured as exhaled volatile compounds (VOCs) and analyzed using as chromatography-ion mobility spectrometry (GC-IMS technology).

Control subjects had less concern about breath malodor, but subjects with PKU were concerned about breath odor and associated this with PS. Study results from the questionnaire suggests that the effects of L-AA and CGMP-AA on exhaled breath are likely to be different, immediately post-consumption. Breath analyzed immediately after consumption of both L-AA and CGMP-AA PS showed an immediate increase in the number of VOC peaks, but these were no longer detectable at 30 min post-consumption.

Longitudinal breath testing showed that there were no significant differences in the number and types of exhaled VOCs compared to controls or between PS. PS are thus shown to have a transient effect on exhaled breath. The timing of PS consumption with other foods or drinks may help to eliminate PS-related unpleasant breath odour.

Journal of Breath Research. 2019 Oct 21;14(1):016001

Glycomacropeptide: Long-Term Use And Impact On Blood Phenylalanine, Growth And Nutritional Status In Children With PKU

Daly A, Evans S, Chahal S, Santra S, Pinto A, Jackson R, Gingell C, Rocha J, Van Spronsen FJ, MacDonald A

The amino acid profile of protein substitutes (including amino acids ratio) requires further study, especially when based on casein glycomacropeptide (CGMP). In this 12-month longitudinal, prospective study, the impact of using a modified CGMP-AA protein substitute (CGMP-AA2) is described and compared with a control group of children taking conventional Phe-free L-AA supplements only. The aim of this study was to evaluate a CGMP-AA2 formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU.

CGMP-AA2 is a flavoured powdered protein substitute containing 20 g of protein equivalent, and 36 mg of Phe per 35 g sachet. Additional essential amino acids were added to provide a similar AA profile to conventional Phe-free L-AA supplements. Fifty children diagnosed by newborn screening with PKU were recruited. At baseline and 26 weeks, morning fasted preprandial venous samples were collected for nutritional markers. Anthropometry, height and weight, together with a stock check of protein substitute usage, diet history, and food frequency questionnaire were collected monthly.

At the end of 52 weeks only 48% of subjects were able to completely use CGMP-AA2 as their single source of protein substitute, without affecting blood phe control At 52 weeks CGMPAA2 provided a median of 75% of the total protein substitute with the remainder being given as L-AA. Within the CGMP-AA2 group, blood Phe increased significantly between baseline and 52 weeks. There were no differences for Phe, Tyr, Phe:Tyr ratio and anthropometry when comparing the control group using L-AA and the CGMP-AA2 group. However, in the same period within the CGMP-AA2 group, blood Phe concentrations, weight and BMI z significantly increased. The median values for all nutritional parameters, measured at baseline and 26 weeks, were all within the reference ranges.

CGMP can impact blood Phe concentrations so should be used with care in young children. On introducing CGMP, especially in young children, blood Phe levels should be closely monitored and it may be that in young children CGMP can only be partially used to meet protein requirements.

Orphanet Journal of Rare Diseases. 2019 Feb 15;14(1):44.

Preliminary Investigation To Review If A Glycomacropeptide Compared To L-Amino Acid Protein Substitute Alters The Pre-And Postprandial Amino Acid Profile In Children With Phenylketonuria

Daly A, Evans S, Pinto A, Jackson R, Ashmore C, Rocha JC, MacDonald A

Protein substitutes are an essential source of synthetic protein in the dietary management of phenylketonuria (PKU). These are either based on solely amino acids without phenylalanine (Phe-free AA) or based on casein glycomacropeptide (cGMP) with added amino acids. cGMP may slow the rate of amino acid (AA) absorption when compared with traditional Phe-free AA, improving nitrogen utilization, decreasing urea production and modifying insulin response. The aim of this study was to compare pre and postprandial AA concentrations in children with PKU, when taking one of protein substitute (Phe-free AA, CGMP-AA1 or CGMPAA2).

The study included 43 children (24 boys), with a median age of 9 years-old (5-16 years). CGMP-AA1 was given to 11 children, CGMP-AA2 to 18 children and 14 Phe-free AA. Quantitative AA was assessed in blood samples at 2 timepoints on one day.: early morning fasting preprandial and 2 hours postprandial. Children had a breakfast with 20 g protein equivalent from protein substitute post fasting blood sample.

All three protein substitutes yielded a significant increase in postprandial AA for all individual AAs. The AA composition of the three different protein substitutes led to higher postprandial AA histidine, leucine and tyrosine in CGMP-AA2 compared to CGMP-AA1, and leucine, threonine and tyrosine higher in GCMP-AA2 compared to Phe-free AA.

The AA composition of CGMP-AA had an influence in 2 hour postprandial AA composition in children with PKU, which suggests that a protein substitute derived from CGMP-AA may be comparably absorbed to Phe-free AA.

Nutrients. 2020 Aug 14;12(8):2443.

The Impact Of The Use Of Glycomacropeptide On Satiety And Dietary Intake In Phenylketonuria

Daly A, Evans S, Pinto A, Jackson R, Ashmore C, Rocha JC, MacDonald A

Protein increases secretion of gastrointestinal hormones and diet-induced thermogenesis, while being the most satiating macronutrient. Phenylketonuria (PKU) restricts natural protein intake, with about 80% of intake being from a synthetic source, which may alter satiety response. Satiety may be enhanced by casein glycomacropeptide (CGMP-AA), a carbohydrate containing peptide and alternative protein substitute (PS) to amino acids (AA), by mechanism of its bioactive properties. The objective of this study was to assess the effect of both amino acid based PS (AA) and CGMP AA when given as a sole source of PS (cGMP100) and a combination of CGMP-AA and AA PS (cGMP50) on satiety, weight and body mass index (BMI).

This was a three-year longitudinal, prospective study with 48 children with PKU. Median ages were 9.2 years for CGMP100 group (n = 13), 7.3 years for CGMP50 group (n = 16), and 11.1 years for AA group (n = 19). Every three months, semi-quantitative dietary assessments and anthropometry (weight, height and BMI) were assessed.

The contribution of macronutrient to total energy intake from protein, carbohydrate and fat was similar within groups. After adjusting for age and gender, there were no apparent difference in energy intake, weight, BMI, incidence of overweight or obesity between groups.

This three year study did not show an indication to support a relationship between cGMP and satiety, which is a complex multi-system process that is not fully understood.

Nutrients 2020 Sep 4;12(9):2704.

Growth And Body Composition In PKU Children— A Three-Year Prospective Study Comparing The Effects Of L-Amino Acid To Glycomacropeptide Protein Substitutes

Daly A, Högler W, Crabtree N, Shaw N, Evans S, Pinto A, Jackson R, Strauss BJ, Wilcox G, Rocha JC et al.

Protein quality and quantity are important factors in determining lean body (muscle) mass (LBM), and body composition and growth are important indicators of long-term health. In phenylketonuria (PKU), protein substitutes provide most of the nitrogen, either as amino acids (AA) or glycomacropeptide with supplementary amino acids (CGMP-AA).

48 children were recruited for a 3-year prospective study investigating the impact of AA and CGMP-AA on body composition and growth. 19 of the patients (median age 11.1 years, range 5–15 years) took AA based protein substitute only. 16 patients (median age 7.3 years, range 5–15 years) took a combination of CGMP-AA and AA based protein substitutes (CGMP50). 13 children (median age 9.2 years, range 5–16 years) took a CGMP-AA based protein substitute only (CGMP100).

A dual energy X-ray absorptiometry (DXA) scan was done at enrolment and 36 months and measured LBM, % body fat (%BF) and fat mass (FM). Height was measured at enrolment, 12, 24 and 36 months.

After adjusting to age, gender, puberty and blood phenylalanine levels no statistically significant differences or correlations were found between the 3 groups for LBM, %BF, FM and height. There was a trend towards children in the CGMP100 group being taller with a change in height z scores (AA 0, CGMP50 +0.4 and CGMP100 + 0.7) with an improved LBM and decreased FM and % BF when compared to the other 2 groups but this was not statistically significant.

After 3 years of follow up there appeared to be no advantage of CGMP-AA compared to AA on body composition. However, a trend towards improved body composition and height growth was observed in those children taking a CGMP-AA based protein substitute as their sole protein substitute requirement, although statistically significant differences were not reached.

Nutrients 2021, 13, 1323.

A Three-Year Longitudinal Study Comparing Bone Mass, Density, And Geometry Measured By DXA, Pqct, And Bone Turnover Markers In Children With PKU Taking L-Amino Acid Or Glycomacropeptide Protein Substitutes.

Daly A, Högler W, Crabtree N, Shaw N, Evans S, Pinto A, Jackson R, Ashmore C, Rocha JC, Strauss BJ et al.

Evidence suggests that in individuals with phenylketonuria (PKU) managed by diet therapy only, areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm.

The aim of this study was to review longitudinal bone mass, density, and geometry in children with PKU managed with diet only, over a 36-month period. The children took either amino acid (L-AA) or casein glycomacropeptide protein substitutes (CGMP-AA) or a combination of both as their main protein source.

A total of 48 subjects completed the study, 19 subjects were recruited into the L-AA group (median age 11.1, range 5–16 years) consuming amino acid-based protein substitutes only, 16 subjects were recruited into the CGMP50 group (median age 7.3, range 5–15years), consuming a combination of CGMP-AA and L-AA based protein substitutes and 13 subjects were recruited into the CGMP100 group (median age 9.2, range 5–16years) consuming a CGMP-AA protein substitute only. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months. Serum blood and urine bone turnover markers (BTM) and blood bone biochemistry were measured at enrolment, 6, 12, and 36 months. Peripheral quantitative computer tomography (pQCT) was measured at 36 months only.

All blood biochemistry markers were within the reference ranges and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2), bone mineral apparent density (L2–L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). The overall bone density values for the groups were below the population mean but within the normal reference values.

In children with PKU taking either a CGMP-AA based protein substitute, an L-AA based protein substitute or a combination of both as their main protein source supported normal bone growth.

Nutrients 2021, 13(6), 2075