The study, “The Impact of a Slow-Release Large Neutral Amino Acids Supplement on Treatment Adherence in Adult Patients with Phenylketonuria,” was published in the journal Nutrients.
Mutations in the PAH gene, the underlying cause of PKU, lead to a significant increase in the levels of the amino acid phenylalanine in the blood. (Amino acids are the building blocks of proteins). The PAH gene has the instructions for making an enzyme that converts phenylalanine into another amino acid, tyrosine.
Some of the amino acids whose concentrations are impaired play an essential role in the normal production of neurotransmitters, the chemical messengers used by nerve cells to communicate.
The gold standard therapeutic approach for patients with PKU is to follow a phenylalanine-restricted diet. However, “adherence to this therapy is difficult, especially for adolescent and adult patients.” In fact, adherence to long-term treatment in developed countries is only around 50%, according to a World Health Organization report.
Supplementation with LNAAs, amino acids carried to the brain using the same transporter protein as phenylalanine, has been suggested for PKU patients who do not adhere to their diets.
LNAAs are likely to reduce the concentration of phenylalanine reaching the brain and promote the increase of other amino acids important for the balanced production of neurotransmitters.
In a prior study, Italian researchers showed that in adult PKU patients, supplementation with a commercial LNAA (called Neutrafenil Micro R, marketed by PIAM Farmaceutici) for one year led to a significant increase in the levels of tyrosine.
However, it remains unknown how well adults with PKU adhere to this LNAA formulation.
To address this knowledge gap, the same team from Italy evaluated 12 adults with classic PKU (ages 19 to 38) followed at the University Hospital of Padova who struggled for more than a year to follow a phenylalanine-restricted diet. All patients had normal intelligence quotient scores (higher than 70) and no history of psychiatric illness.
They received the slow-release LNAA (again Neutrafenil Micro R) at a daily dose of 1 gram per kilogram (kg) of body weight, divided in three daily doses at main meals (breakfast, lunch and dinner) for a year. This LNAA formulation completely replaced their prior amino acid regimens, but no changes were made to low-protein foods and they could still receive vitamin and other micronutreient supplementation. Patients were asked to maintain food habits.
Patients were assessed for phenylalanine and tyrosine levels every two weeks via collection of dried blood spots in their homes.
Medication adherence was measured with the Morisky Green Levine Medication Adherence Scale, ranging from a score of zero (high adherence) to four (low adherence). Quality of life was assessed using the phenylketonuria-quality of life (PKU-QoL) questionnaire.
Before beginning LNAA supplementation, three patients reported “medium” and nine “low” adherence to medication. More than half (60%) reported full adherence in the previous four weeks.
After 12 months of LNAA, all participants reported high adherence to medication, with 96% reporting full adherence.
While the levels of phenylalanine did not change over the duration of the study, the researchers saw a significant increase in the blood levels of tyrosine in 11 participants, from a mean of 59 micromol (umol)/L to 75 umol/L.
All patients reported significant improvements in quality of life, including fewer episodes of aggressiveness and irritability. Patients also had fewer complaints related to their palate.
Overall, these results suggest that “LNAAs may give patients a further opportunity to improve medication adherence and, consequently, their QoL [quality of life],” the investigators concluded.
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