Protein intake and physical activity are associated with body composition in individuals with phenylalanine hydroxylase deficiency

Mol Genet Metab. 2017 Jun;121(2):104-110. doi: 10.1016/j.ymgme.2017.04.012. Epub 2017 Apr 28.


Objective: Determine whether body composition as it relates to dietary protein in patients with phenylalanine hydroxylase (PAH) deficiency is associated with genotype, dietary factors, and lifestyle choices.

Methods: We examined associations between protein intake (intact and medical foods: MF) and body composition in PAH-deficient patients along with, physical activity, and genotype. Protein intakes (total, intact, and MF) were analysed from three-day food records with Nutrition Data System for Research (NDSR) in 59 children and 27 adults (N=86, median age=16.0years). The severity of PAH deficiency was classified using the genotype assigned value method (AV sum). Physical activity was assessed using a study-developed question (light vs. intense activity). Body composition was measured by DXA, including android:gynoid ratio (A:G), fat-free mass index (FFMI), fat mass index (FMI), and FMI:FFMI ratio.

Results: High intact protein intake was associated with high FFMI (rs=0.75, p=0.008) and low FMI:FFMI (rs=-0.59, p=0.04) in adults. Only in children, MF protein (rs=0.38, p=0.04) was directly proportional to FFMI. Median intact protein intakes of adults (25.1 vs. 9.9g/d, p<0.001) and children (11 vs. 6g/d, p<0.001) were higher than prescribed. Only in adults, the actual median MF protein intake was lower than prescribed (53 vs. 60g/d, p=0.03). In adults and children, light activity was associated with higher fat mass indices compared to intense activity (adults: FMI:FFMI: β=1.1, p=0.001, children: FMI:FFMI: β=1.1, p=0.007; FMI β=2.1, p=0.01; A:G β=1.1, p=0.04). All associations remained significant after covariate adjustment. Genotype was not associated with body composition.

Conclusions: Although fat-free mass in adults was positively associated with intact protein intake, it should be consumed as prescribed per individual tolerance to maintain plasma Phe concentrations within treatment range. In children, total protein maximized with MF should be encouraged to promote lean mass. Nutrition counselling could be complemented with physical activity recommendations for optimal clinical outcomes.

Trial registration: NCT00688844 NCT01659749.

Keywords: Body composition; Genotype; Intact protein; Medical foods; Phenylalanine hydroxylase deficiency; Physical activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Body Composition*
  • Body Mass Index
  • Child
  • Child, Preschool
  • Dietary Proteins / administration & dosage*
  • Dietary Proteins / analysis
  • Exercise*
  • Female
  • Genotype
  • Humans
  • Life Style
  • Male
  • Middle Aged
  • Nutrition Therapy
  • Obesity
  • Phenylketonurias / genetics*
  • Phenylketonurias / metabolism
  • Phenylketonurias / physiopathology*
  • Young Adult


  • Dietary Proteins

Associated data