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Unique whey Protein is Promising Supplement for Strict PKU Diet

Science Daily
February 4, 2008

Individuals with a rare genetic condition known as phenylketonuria, or PKU, receive a difficult-to-follow prescription. They must severely limit their consumption of protein, completely avoiding mealtime staples such as meat, cheese and even bread. Not surprisingly, for many, diet is a constant struggle.

In an effort to expand their dietary options, a team of University of Wisconsin-Madison scientists is assessing a unique protein found only in whey, the liquid byproduct of cheese-making, that appears to be safe for this group to eat. As published recently in the Journal of Nutrition, the team found that this protein--when supplemented with a few amino acids--supports the growth of young, normal mice. More importantly, mice with a version of PKU fared well on this whey protein diet and had relatively low levels of PKU-associated toxins in their brain tissue and blood.

These findings open the door to the possibility that individuals with PKU will be able to eat foods enriched with the whey protein.

"We did these studies in mice to show that (eating this protein) is going to be feasible in humans," says Denise Ney, a professor of nutritional sciences who headed up the study, which was funded by the UW-Madison Graduate School and the U.S. Department of Agriculture. "It's so important to individuals on this diet to have new options, to have their diet liberalized. It's a quality-of-life issue."

There are around 15,000 people in the United States with PKU. From birth, they lack the enzyme responsible for breaking down phenylalanine, one of the 20 major amino acids that form the proteins we eat in everyday foods. They must avoid protein because, while small amounts of phenylalanine are required for life, excess amounts stay in their bodies indefinitely and interfere with brain function. Those who go off-diet often suffer from concentration problems and depression. A few even sustain permanent brain damage.

Instead of eating protein directly, people with PKU drink a foul-tasting cocktail of amino acids to meet most of their body's daily protein needs. It tastes so bad that many struggle to drink enough to meet their doctor's orders.

Ney hopes to reduce reliance on this cocktail by offering an alternative--foods and beverages made with glycomacropeptide, the only known dietary protein that is phenylalanine-free. Mark Etzel, a UW-Madison food engineer and fellow co-author on the paper, developed a method to purify this unique protein from cheese whey.

"Glycomacropeptide is lousy from the standpoint of protein quality. It doesn't have the right proportion of essential amino acids," says Ney. "However, we show that by supplementing it with the right amino acids, the mice grow just fine. This establishes the nutritional adequacy of this diet."

Her team also looked at the brains of mice with PKU, where phenylalanine causes problems. "Perhaps the most interesting observation about the mice that were fed glycomacropeptide is that they had a 20 percent decrease in phenylalanine in their brains (compared to those fed the equivalent of the traditional amino-acid diet prescribed to humans). That's a pretty good drop, and we saw it consistently in five different areas of the brain."

Phenylalanine was also lower in the blood of these mice, by about 11 percent.

Upon learning about these positive results, various grassroots organizations that support the PKU community decided to fund this project, helping the UW-Madison team move more quickly in the direction of real-world applications. Already, Kathy Nelson, a researcher at the Wisconsin Center for Dairy Research, has created a line of glycomacropeptide-fortified foods, including pudding, fruit rolls, crackers and an assortment of flavorful drinks. Prototypes are currently being tested in a human clinical study funded by the National Institutes of Health, and the preliminary results look promising, says Ney.

In the future, Ney thinks this protein could replace about half of a person's daily dose of the amino acid drink. Most people with PKU drink two or three cups per day. By consuming a glycomacropeptide-fortified pudding cup, fruit roll or sports drink, they may be able to drink just one or two.

This is exactly what Ann Zimmerman of Middleton, Wis. would like to see. Her 10-year old daughter Jessica recently began refusing to drink her amino acid drink at school, after getting teased a few times. "While we wait for treatments that address the underlying problem of PKU," says Zimmerman, "glycomacropeptide is what we need."

Adapted from materials provided by University of Wisconsin-Madison, via EurekAlert!, a service of AAAS.

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