A Cross-Sectional Study on Protein Substitutes for Paediatric Phenylketonuria Diet: Time to Pay Attention.

Introduction: Protein substitutes (PSs) free of phenylalanine (Phe) represent the primary source of proteins and micronutrients in dietary management of classical Phenylketonuria (PKU). Over the last few years, the composition of PSs has undergone rapid and significant improvements, including the development of slow-release amino acid technologies, the introduction of glycomacropeptide-based products, as well as enhancements in taste and the variety of available formulations. However, their micronutrient content has received limited attention. This work aims to analyse the micronutrient composition of all PS formulations available in Italy for paediatric PKU patients and compare their micronutrient contribution to the recommended dietary allowance (RDA) and assess variability among products and age groups. Materials and

Methods: The content of 28 micronutrients was analysed in 63 PSs, grouped according to the age ranges defined by the RDA guidelines: 0-6 months, 6-12 months, 1-3 years, 3-8 years, 8-14 years. The micronutrient content was standardised for 10 g of protein equivalent (PE).

Results: Compared to the RDA, many micronutrients were found to be over-supplemented across all age groups, particularly in the 0-6 month group, where peak levels were observed for vitamin K, chromium, and manganese. The 1-3 age group showed the lowest levels of supplementation, with most micronutrients falling within the sub-supplementation range. The variability in supplementation among PSs was broad and showed the highest values in the latter age ranges, reaching maximum levels for biotin and copper. Among different ages, the variability was higher in the first two age ranges, particularly for vitamin A. Choline is not supplemented in many PSs across different age ranges.

Conclusions: Many micronutrients supplemented in the PSs exceed the RDA for all age groups, with high variability among different PSs and age groups. When prescribing a PS, the daily amount of synthetic proteins of the diet should be considered in order to evaluate the real daily intake of micronutrients in a PKU diet.