New Clues to Healthy Bones for People with PKU

For approximately 15,000 people in the United States, a vital amino acid can become their worst enemy.

Individuals with the metabolic disorder phenylketonuria, or PKU, cannot metabolize the amino acid phenylalanine. Without careful dietary management, it can accumulate at high levels in their blood, leading to cognitive impairment, seizures, and other serious health problems.

There is no cure for PKU, and patients must adhere to a lifelong diet of medical foods that contain protein but are low in phenylalanine. Traditionally, these medical foods have been made using synthetic protein substitutes derived from mixtures of amino acids. But these amino acid- based medical foods could be contributing to the skeletal fragility seen in many PKU patients, according to a new study led by nutritional sciences professor Denise Ney and Bridget Stroup PhD’17.

The researchers also discovered that an alternative medical food, developed by Ney from a protein called glycomacropeptide (GMP) — a natural byproduct found in the whey extracted during cheese production — could allow PKU patients to manage their diets without compromising their bone health. This study represents the first human clinical trial comparing how different PKU-specific diets affect the bone health of people living with the disease.

Ney helped develop GMP-based foods for PKU patients just over a decade ago. In subsequent studies, she has shown that mice fed GMP-based diets have larger and stronger bones than mice on amino acid based diets. “It was a vital clue that there could be a link between amino acid medical foods and the skeletal fragility seen in many PKU patients,” says Ney, a researcher at UW–Madison’s Waisman Center.

For the current study, Ney and her research team assigned eight individuals with PKU to a diet of amino acid-based medical foods before switching them to GMP-based foods with a low dietary acid load. The researchers found that PKU patients had higher amounts of calcium and magnesium in their urine while on the amino acid based diet, a sign of bone breakdown, which can impair bone health.

“The amino acid medical foods have high acid loads, which can change the overall acid-base balance within the body,” Stroup says. Bones are able to buffer high acid loads in the body, but over time this leads to a breakdown and release of minerals. On the other hand, Glytactin (the trademarked brand name for the formulation used in the study) GMP medical foods do not have high acid loads.

Although the researchers did not directly measure bone breakdown and density in this study, other studies have found that reducing the acid content of diets leads to lower urine-calcium excretion and increased bone density.

These findings, Ney says, could also help patients with other kinds of metabolic disorders, like maple syrup urine disease. And although the sample size of the study was relatively small, it is typical of investigations into rare diseases; Ney hopes to secure additional funding for further study.

Ney is working on a larger clinical trial to study the metabolism of calcium and other minerals in PKU patients consuming amino acid or GMP medical foods. “We will be looking at bone health and also other physiological aspects, such as the gut microbiota,” she says.