Advances in the nutritional and pharmacological management of phenylketonuria

Abstract

Structural Abstract Purpose of review The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). Recent findings Glycomacropeptide (GMP), a whey protein produced during cheese production, is a low-phe intact protein that represents a new dietary alternative to synthetic amino acids (AAs) for people with PKU. Skeletal fragility is a long-term complication of PKU that based on murine research, appears to result from both genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated with the GMP diet, compared with an AA diet, allowing greater radial bone growth. Pharmacologic therapy with tetrahydrobiopterin (BH4), acting as a molecular chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in some individuals. Large neutral AAs (LNAA) inhibit phe transport across the intestinal mucosa and blood brain barrier; LNAA are most effective for individuals unable to comply with the low-phe diet. Summary Although a low-phe synthetic AA diet remains the mainstay of PKU management, new nutritional and pharmacological treatment options offer alternative approaches to maintain lifelong low phe concentrations. GMP medical foods provide an alternative to AA formula that may improve bone health, and BH4 permits some individuals with PKU to increase tolerance to dietary phe. Further research is needed to characterize the long-term efficacy of these new approaches for PKU management.

Emerging trends in nutraceutical applications of whey protein and its derivatives

“…It was reported that glycomacropeptide diet ameliorated this condition. Bone health improved and higher radial bone growth was observed (Ney et al 2014). The above studies indicate that glycomacropeptide is a better alternative to the regular synthetic amino acids, for it improves the taste and satiety of diet leading to better patient compliance (Strisciuglio and Concolino 2014).…”

Functional food relevance of whey protein: A review of recent findings and scopes ahead

“…Osteopenia characterized by bone mineral deficiency is a symptom of phenylketonuria. Glycomacropeptide diet restored the bone mineral density to normalcy (Ney, Blank, & Hansen, 2014). The above studies indicate that gycomacropeptide is a better alternative to the conventional synthetic amino acids.…”

Alternative Therapies for PKU

“…The product is rich in valine, isoleucine, and threonine but has a very low amount of tyrosine, tryptophan, arginine, cysteine, and histidine; thus, supplementation with those essential amino acids is necessary to provide an intact protein with high biological value. 26,27 Studies in PKU mice show that GMP feeding reduces metabolic activity and attenuates immune responses due to high PHE levels. The murine model receiving GMP, lowered PHE levels in blood and brain, and showed increased lean mass and improved bone strength.…”