Complications of the Low Phenylalanine Diet for Patients with Phenylketonuria and the Benefits of Increased Natural Protein

Abstract

Phenylketonuria (PKU) is an inherited disorder in which phenylalanine (Phe) is not correctly metabolized leading to an abnormally high plasma Phe concentration that causes profound neurologic damage if left untreated. The mainstay of treatment for PKU has centered around limiting natural protein in the diet while supplementing with medical foods in order to prevent neurologic injury while promoting growth. This review discusses several deleterious effects of the low Phe diet along with benefits that have been reported for patients with increased natural protein intake while maintaining plasma Phe levels within treatment guidelines.

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

“…Many somatic comorbidities have been identified in retrospective claims-based studies, out of which the expert panel considered overweight/obesity, osteopenia and gastrointestinal issues to be potentially associated with long-term reliance on MNT [ 16 , 17 ]. A similar observation was made in a recent review in describing the possible link between protein restriction and physical health manifestations in PKU [ 29 ]. However, as for all PKU-associated comorbidities, it remains impossible to determine whether or not these relate to blood Phe, the restrictive nature of MNT as the primary intervention, suboptimal adherence to MNT or any other yet-to-be-identified pathophysiological mechanism.…”

“…In addition to the burden of restricting dietary Phe, the consumption of protein substitutes/medical foods can interfere significantly with activities of daily life (e.g., work, educational activities, sports, travelling and dining out) and lead to dietary stigma and feelings of social exclusion [ 24 , 25 , 26 , 27 , 28 ]. Other obstacles limiting adherence in the long term include the financial cost and time burden associated with the daily intake of protein substitutes/medical foods and the lack of palatability, as described further in the topic on the burden of long-term reliance on MNT [ 24 , 28 , 29 ]. Statement #2 Consensus For adults with PKU on MNT, the ability to maintain blood Phe concentrations ≤360 µmol/L throughout life is limited to a minority of patients having a milder disease phenotype, significant discipline in the setting of adequate resources and continued access to care, or to temporary circumstances of intensive medical involvement and support, such as pregnancy.…”

“…It has been suggested that both elevated blood Phe concentrations and severe protein restriction together with the intake of synthetic protein substitutes/medical foods may also compromise a patient’s physical health [ 29 ]. Many somatic comorbidities have been identified in retrospective claims-based studies, out of which the expert panel considered overweight/obesity, osteopenia and gastrointestinal issues to be potentially associated with long-term reliance on MNT [ 16 , 17 ].…”

Evaluation of a New ‘Mix-In’ Style Glycomacropeptide-Based Protein Substitute for Food and Drinks in Patients with Phenylketonuria and Tyrosinemia

“…The low-Phe and -Tyr diets prescribed for patients with classical PKU and TYR are limited to a narrow selection of food groups, including fruits, most vegetables, sugars, pure fats, and special low-protein foods. Most high-protein foods, such as dairy products, meats, legumes, nuts, and most grains, are typically avoided due to the high content of Phe and Tyr, which creates challenges both nutritionally and in terms of food palatability and variety [ 11 , 12 ]. A protein substitute is essential for most patients with PKU and TYR, supplying classical patients with 75% to 85% of daily protein needs [ 11 , 13 ] and as an essential source of nutrients for which patients are at risk of being deficient due to their restrictive diet: vitamins (e.g., B12, D), minerals (e.g., calcium, selenium), and long-chain polyunsaturated fats (e.g., DHA) [ 11 , 14 ].…”

“…Most high-protein foods, such as dairy products, meats, legumes, nuts, and most grains, are typically avoided due to the high content of Phe and Tyr, which creates challenges both nutritionally and in terms of food palatability and variety [ 11 , 12 ]. A protein substitute is essential for most patients with PKU and TYR, supplying classical patients with 75% to 85% of daily protein needs [ 11 , 13 ] and as an essential source of nutrients for which patients are at risk of being deficient due to their restrictive diet: vitamins (e.g., B12, D), minerals (e.g., calcium, selenium), and long-chain polyunsaturated fats (e.g., DHA) [ 11 , 14 ]. Consequently, poor adherence to protein substitutes can lead not only to high blood Phe levels but also to malnutrition [ 14 , 15 ].…”