Whey May Help Manage PKU

Food products made from a specific protein found in whey can safely be part of a more palatable diet for individuals diagnosed with phenylketonuria (PKU), according to a new clinical trial led by researchers at the University of Wisconsin (UW)-Madison and Boston Children's Hospital.

"Our findings could also lead to increased insurance coverage for 'medical foods' that individuals with PKU need to lead healthful lives," says Denise Ney, PhD, RD, lead author of the study. Ney is the Billings-Bascom Professor of Nutritional Sciences in the College of Agricultural & Life Sciences at UW-Madison and a researcher at the UW's Waisman Center.

PKU is a rare disease that affects approximately 1 in 15,000 people in the United States. Individuals with PKU can't metabolize the amino acid phenylalanine. If left untreated, PKU can lead to the accumulation of dangerous levels of the amino acid in the body; this can cause intellectual disabilities, seizures, and other serious health problems.

There's no cure for PKU, and individuals diagnosed with it find themselves in a double bind. The only way to manage the disease is to adhere strictly to a lifelong diet low in phenylalanine. But almost all naturally occurring proteins contain phenylalanine; having to avoid it makes it very difficult for individuals with PKU to consume enough protein.

Traditionally, synthetic protein substitutes made from mixtures of amino acids have been used to create nutritional formulas that PKU patients need to drink daily to ensure they get enough protein in their diets. These protein substitutes can only be consumed as a formula, tablets, or gel and cannot be made into other food products such as bars or spreads.

"Also, they're often described as 'smelling bad and tasting worse' and it can be difficult for adults, let alone children, to stick to this diet day after day," Ney says.

To overcome some of the shortcomings of the synthetic protein diet, Ney has worked to develop safer and more palatable options for PKU patients. She focused on a protein called glycomacropeptide (GMP), a natural leftover in the whey created during production of cheese.

GMP is unusual in that it's the only known natural protein that contains no phenylalanine in its pure form. The small amounts of the amino acid in food products made using GMP come from other proteins left over from the process used to purify GMP from whey.

After promising results using animal models and a prior clinical trial to establish the safety of GMP medical foods, Ney and her colleagues in Boston initiated a clinical trial, which followed 30 individuals with PKU over several weeks.

The results showed that trial participants who consumed GMP foods had levels of phenylalanine in their blood similar to those of participants who consumed the traditional amino acid formula, even though GMP foods contain more phenylalanine than the synthetic amino acids.

They also rated the GMP foods as more palatable—a development that could increase how strictly PKU patients stick to their diets—and showed fewer negative side effects, such as persistent hunger and gastrointestinal symptoms, compared with participants on the traditional synthetic amino acid diet.

"We provide evidence that GMP medical foods provide a safe and acceptable alternative to synthetic formulas for managing PKU," Ney says.

Medical foods made using GMP are currently more expensive than the traditional amino acid formula, but Ney believes that with wider usage and adoption of the new foods, the price difference will diminish.

Screening and management of PKU has a long and storied connection to Wisconsin. Harry Waisman, MD, PhD, a researcher and clinician—after whom the Waisman Center is named—was instrumental in initiating the testing of infants for PKU and treating individuals with the disorder throughout the state.

"I think this research exemplifies the Wisconsin Idea—developing a way to better manage a disease that cuts across demographics and nationalities using a byproduct of cheese production," Ney says.

— Source: University of Wisconsin-Madison