Phenylketnouria (PKU) is an inborn error of phenylalanine (phe) metabolism screened for at birth in the United States and Europe. Those with PKU have a defect in the ability to convert the essential amino acid (AA) phe to tyrosine. With a normal diet, elevated levels of phe in the blood of these individuals is toxic to the brain and results in severe cognitive impairment (NIH, 2000). To prevent brain damage, a diet low in phe that severely restricts intake of natural dietary protein and requires a specialized, phe-free AA formula must be initiated shortly after birth and followed lifelong (MacLeod and Ney, 2010). Unfortunately, compliance with the diet after early childhood is poor, resulting in neuropsychological deterioration (Enns et al., 2010). The difficulty of the PKU diet reflects its highly restrictive nature, as well as the requirement to consume 24–32 oz per day of a phe-free AA formula to meet protein needs. The taste and smell of the AA formulas can be offensive; new dietary options are needed to improve the acceptability and variety of the low-phe diet.
Glycomacropeptide (GMP), a 64-amino acid glycophosphopeptide cleaved from κ-casein during cheese making, is found in bovine whey (Laclair et al., 2009). GMP is the only known dietary protein that in its pure form contains no phe, and thus, foods made from GMP provide an alternative to synthetic AA-based formulas. GMP has functional properties suitable for making low-phe foods and can be made into a variety of highly palatable products high in protein but low in phe. Our research shows that GMP foods are highly acceptable alternatives to AA formulas and that they improve protein and phe utilization (Ney et al., 2009; Van Calcar et al., 2009). Using Glytactin™, a patent-pending blend of GMP and essential AA, Cambrooke Foods, Boston, Mass.(www.cambrookefoods.com), has successfully introduced the complete formula BetterMilk™ and the sports drink Restore™ to the PKU community with plans to offer additional GMP products. Prior to conducting clinical studies in humans with PKU, we established in PKU mice that GMP can be formulated into a nutritionally adequate diet that supports growth and reduces phe concentrations in plasma and brain (Ney et al., 2008; Solverson et al., 2012). The short-term safety of GMP was demonstrated in our inpatient metabolic study where 11 subjects with PKU followed a GMP diet in which all of their usual AA formula was replaced with intact protein from GMP, supplemented with limiting AA for 4 days (Van Calcar et al., 2009). Results for plasma insulin concentration and blood urea nitrogen suggest protein from GMP was retained better by the body than the equivalent protein provided by the AA formula. This improved protein retention reflects the fact that GMP is an intact protein with slower digestion and appearance of AA in plasma compared to synthetic AA, which appear in plasma rapidly after ingestion, followed by hepatic uptake and degradation to urea. In our first clinical study, plasma levels of phe were not statistically different with the GMP and AA diets, although plasma levels of threonine and the branched chain AAs were significantly increased in association with the high content of these essential AAs in GMP. However, in one subject who safely followed the GMP diet for 10 weeks at home, a significant 14% reduction in mean blood phe concentration relative to phe intake was noted compared to the AA diet (Ney et al., 2009).
In addition to its unique application to PKU, GMP demonstrates several interesting biological properties, including inhibition of bacterial and viral adhesions, modulation of immune function, and promotion of satiety (Brody, 2000; Krissansen, 2007). Research demonstrates that a GMP meal improves satiety with sustained suppression of ghrelin compared with an AA meal in PKU subjects (MacLeod et al., 2011), modulates food intake in control subjects, and reduces body fat content in rodents. Moreover, a GMP diet normalizes the metabolic stress that is reflected in increased renal workload and systemic inflammation when feeding an AA diet in PKU mice (Solverson et al., 2012).
In summary, foods made with the whey protein GMP provide a physiologic source of low-phe dietary protein that is an alternative to synthetic AA formula for those with PKU. Our research suggests that GMP foods improve protein retention, increase satiety, and enhance the taste, variety, and convenience of the PKU diet. Taken together, GMP may improve health and quality of life for those with PKU.
Denise M. Ney, Ph.D., R.D.,
Billings Bascom Professor of Nutritional Sciences,
University of Wisconsin, Madison, Wis.,
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