Protein Substitutes in PKU; Their Historical Evolution

Abstract

Protein substitutes developed for phenylketonuria (PKU) are a synthetic source of protein commonly based on L-amino acids. They are essential in the treatment of phenylketonuria (PKU) and other amino acid disorders, allowing the antagonistic amino acid to be removed but with the safe provision of all other amino acids necessary for maintaining normal physiological function. They were first formulated by a chemist and used experimentally on a 2-year-old girl with PKU and their nutritional formulations and design have improved over time. Since 2008, a bioactive macropeptide has been used as a base for protein substitutes in PKU, with potential benefits of improved bone and gut health, nitrogen retention, and blood phenylalanine control. In 2018, animal studies showed that physiomimic technology coating the amino acids with a polymer allows a slow release of amino acids with an improved physiological profile. History has shown that in PKU, the protein substitute’s efficacy is determined by its nutritional profile, amino acid composition, dose, timing, distribution, and an adequate energy intake. Protein substitutes are often given little importance, yet their pharmacological actions and clinical benefit are pivotal when managing PKU.

Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis

“…Due to concerns over increasing obesity in PKU, industry has reformulated many of their PS, adding less CHO to their products [21]. Furthermore, a higher prevalence of overweight in patients with PKU is used to support the need for alternative treatments, even though a systematic analysis of published data is not available to verify this claim.…”

Effect of nutritional intervention on nutritional status among children with disorders of amino acid and nitrogen metabolism (AANMDs): A scoping review

“…By adopting the review protocol described in PRISMA-ScR (PRISMA extension for Scoping Reviews), this scoping review successfully addressed and detailed the evolution of nutritional interventions for AANMDs by reviewing literature published over the past 20 years. Unlike existing studies that only address the historical evolution, dosage, and distribution of protein substitutes among PKU patients (43,44), this scoping review contributes to existing knowledge by exploring multiple nutritional interventions and their impact on the nutritional indices of different types of AANMDs instead of a single disorder.…”

Glycomacropeptide in PKU—Does It Live Up to Its Potential?

“…They are usually supplemented with vitamins, minerals and trace elements, and may contain essential and/or long chain fatty acids and prebiotics. In 1953, the first protein substitute was made using a low phenylalanine hydrolysed casein [2,3]; subsequently, the number and type of manufactured preparations have exponentially increased [4]. In 2008, CGMP, a by-product of whey from the manufacture of cheese, was introduced as an alternative protein substitute to L-AAs, but it is still unclear if this protein source has any advantage over conventional L-AAs in the dietary management of PKU.…”