Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

Abstract

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.

Sex effects of dietary protein source and acid load on renal and bone status in thePahenu2mouse model of phenylketonuria

“…The AA and mineral content of the analyzed diets are described in Tables and , respectively. Calculation of the potential renal acid load of the four diets, as previously described (Stroup et al ), suggested that the dietary acid load of the BAA diet was reduced to nearly neutral compared to the high‐acid AA diet (Fig. A); the casein diet was neutral and GMP diet was alkaline.…”

“…In addition, femurs from Pah −/− mice are weaker and show lower bone mineral content (BMC) than femurs from WT mice, and this bone phenotype is exacerbated by the low‐Phe, high‐acid AA diet (Solverson et al ). In eight human subjects with PKU, we demonstrated threefold greater renal net acid excretion with ingestion of high‐acid AA medical foods, which could be ameliorated by ingestion of the low‐acid GMP medical foods (Stroup et al ). In this same study, proteinuria and hyperexcretion of urinary creatinine were observed in 38–63% of subjects with PKU with self‐reported lifelong compliance with high‐acid AA medical foods (Stroup et al ).…”

“…In eight human subjects with PKU, we demonstrated threefold greater renal net acid excretion with ingestion of high‐acid AA medical foods, which could be ameliorated by ingestion of the low‐acid GMP medical foods (Stroup et al ). In this same study, proteinuria and hyperexcretion of urinary creatinine were observed in 38–63% of subjects with PKU with self‐reported lifelong compliance with high‐acid AA medical foods (Stroup et al ). Consistent with this evidence of renal dysfunction in humans with PKU, reduced glomerular filtration rate (GFR) and increased urinary calcium excretion were correlated with graduated increases in ingestion of elemental AAs from medical foods in 67 adolescents and adults with PKU (Hennermann et al ).…”

“…At the same time each morning, the following parameters were assessed: body weight, food intake, water intake, urine volume, and urine pH. Urine samples were stored at −20°C and concentrations of renal net acid and ammonium in urine were measured using titrations as previously described (Stroup et al ).…”

“…The cornerstone of PKU management is life‐long adherence to a low‐Phe diet restricted in protein from all foods, except limited amounts from fruits and vegetables, and supplemented with low‐Phe amino acid (AA) medical foods or glycomacropeptide (GMP) medical foods to provide the majority of dietary nitrogen and micronutrients (Robert et al ; Evans et al ; Singh et al ; Ney et al ; Singh et al ; Pinto et al ; Stroup et al , ). Evidence in humans with PKU and the Pah enu2 murine model of Pah deficiency shows an association between long‐term adherence to a low‐Phe diet supplemented with AAs and the presence of chronic kidney disease (Hennermann et al ; Stroup et al ; Burton et al ), as well as skeletal fragility characterized by low bone mineral density (BMD) and increased risk of fractures (Modan‐Moses et al ; Groot et al ; Hansen and Ney, ; Coakley et al ; Choukair et al ).…”