Using Glycomacropeptide (GMP) for PKU Diet Treatment
By Sandy van Calcar, MS, RD, Sally Gleason, MS, RD, Angela Hall, Kathy Nelson, and Denise Ney, PhD, Biochemical Genetics Program, Waisman Center, Department of Nutritional Sciences and Center for Dairy Research, University of Wisconsin-Madison
From the Winter 2007 issue of National PKU News.
In previous National PKU News articles (Fall 2000 and Spring/Summer 2002),
Dr. Mark Etzel of the Department of Food Science at the University of Wisconsin-Madison
reported about a potential new product that can be used in the treatment
of PKU called glycomacropeptide (GMP).
Studies in PKU MiceBefore any human studies with GMP were planned, we completed several studies with PKU mice that were fed a low-phe diet, with either GMP or amino acids as the primary protein source. The two groups of mice received the same amount of calories, protein, and phe. The mice grew and thrived equally well and were comparable to non-PKU mice that received a typical mouse diet.
GMP is the only known naturally occurring dietary protein that is low in phe. Besides a low phe content, it is also undesirably low in tyrosine and four other amino acids. To compensate, we needed to add extra tyrosine and the other four amino acids to the GMP formula for the mice. In contrast, GMP has a high content of two amino acids, threonine and isoleucine. In fact, the threonine content of GMP is about three times what you would find in the amino acid mix of standard PKU formulas. This high threonine content actually may have a positive effect on blood phe levels. In our studies, we found that PKU mice fed GMP formula had plasma phe levels that were, on average, 10% lower than mice fed an amino acid formula.
These studies told us that using GMP as a protein source did not harm the PKU mice and may even have had a positive effect by reducing plasma phe levels more than we saw with the amino acid-based formula.
GMP Foods and BeveragesVarious foods and beverages containing GMP have been developed in the Food Applications Laboratory at the Wisconsin Center for Dairy Research (CDR) on the University of Wisconsin campus. Foods include GMP pudding (chocolate, strawberry), fruit leather, and crackers. Beverages made with GMP include a flavored beverage (chocolate, strawberry, and caramel) and a GMP sports drink (orange, mango peach, and black cherry). Also, Cambrooke Foods has developed a granola-like snack bar with GMP. We have completed several taste tests with individuals of different ages, both with and without PKU. The GMP products have been well accepted by both groups; the most popular have been the puddings. The CDR is currently working on other products using GMP, which could increase the variety of protein sources for those with PKU.
GMP products are not phe-free like current amino acid-based medical foods used in the PKU diet because the GMP itself contains small amounts of phe. In addition, other ingredients needed to make the products often contain phe. So, for example, when using Dr. Etzelís purified GMP, Ĺ cup of strawberry pudding contains 45 mg phe and 1 cup (8 oz.) of the sports drinks contain 20 mg phe. But the pudding provides 5.6 gm of protein and the sports drink provides 8 gm of protein. This protein in GMP could reduce the amount of PKU medical foods that would be required to meet the total protein needs of someone with PKU. If GMP can be purified further, the amount of phe in these products would decrease, but the amount of phe would still need to be considered in each individualís overall phe prescription.
Clinical StudiesWith the grant from the NIH, we have started a metabolic study using GMP in the diets for those with PKU (age range 8 to 30 years). This part of the study includes 15 subjects and 5 have completed the study so far. For this study, each subject consumes a diet with his or her usual amount of phe and medical food for 4 days. Then for the next 4 days, the diet is changed so that all of the protein from medical food is replaced with GMP products. We measure and provide all of the food during the 8-day study so that the amount of phe and calories is exactly the same on all days. For the last 6 days, each subject comes to Madison and stays in the GCRC (which stands for the General Clinical Research Center at the University of Wisconsin Hospital and Clinics). Each day in the GCRC we measure plasma amino acids (which includes a phe level) and various other labs such as glucose (blood sugar), liver function tests, and measures of protein status. At the end of the first 4 days on the amino acid diet and then again after 4 days on the GMP diet, we measure each subjectís phe level in his/her brain tissue by Magnetic Resonance Spectroscopy (MRS). MRS is a procedure very similar to an MRI scan that is routinely used in a hospital setting to view different structures of the brain.
Preliminary data after the first 5 subjects indicates that no adverse effects occur when subjects replace all of their amino acid formula with GMP for 4 days. We hope to report the effect of GMP on amino acid levels and brain phe concentrations after all 15 subjects have completed the trial. We also plan an outpatient study to see if GMP products, when taken on a long-term basis, can help people with higher phe levels improve their phe control and help make it easier for those who are off diet to return to the diet.
Last update: February 2008
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