title: New stable isotope method to measure protein digestibility and response to pancreatic enzyme intake in cystic fibrosis.
abstract: OBJECTIVE
  Adequate protein intake and digestion are necessary to prevent muscle wasting in cystic fibrosis (CF). Accurate and easy-to-use methodology to quantify protein maldigestion is lacking in CF.
  
  
  OBJECTIVE
  To measure protein digestibility and the response to pancreatic enzyme intake in CF by using a new stable isotope methodology.
  
  
  METHODS
  In 19 CF and 8 healthy subjects, protein digestibility was quantified during continuous (sip) feeding for 6 h by adding (15)N-labeled spirulina protein and L-[ring-(2)H5]phenylalanine (PHE) to the nutrition and measuring plasma ratio [(15)N]PHE to [(2)H5]PHE. Pancreatic enzymes were ingested after 2 h in CF and the response in protein digestibility was assessed. To exclude difference in mucosal function, postabsorptive whole-body citrulline (CIT) production rate was measured by L-[5-(13)C-5,5-(2)H2]-CIT pulse and blood samples were taken to analyze tracer-tracee ratios.
  
  
  RESULTS
  Protein digestibility was severely reduced in the CF group (47% of healthy subjects; P < 0.001). Intake of pancreatic enzymes induced a slow increase in protein digestibility in CF until 90% of values obtained by healthy subjects. Maximal digestibility was reached at 100 min and maintained for 80 min. Stratification into CF children (n = 10) and adults showed comparable values for protein digestibility and similar kinetic responses to pancreatic enzyme intake. Whole-body citrulline production was elevated in CF indicating preserved mucosal function.
  
  
  CONCLUSIONS
  Protein digestibility is severely compromised in patients with CF as measured by this novel and easy-to-use stable isotope approach. Pancreatic enzymes are able to normalize protein digestibility in CF, albeit with a severe delay. Registration ClinicalTrials.gov = NCT01494909.
authors.affiliation: Center for Translational Research in Aging & Longevity, Dept. Health and Kinesiology, Texas A&M University, College Station, TX, USA; Center for Translational Research in Aging & Longevity, Dept. Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: mpkj.engelen@ctral.org.
authors.forename: M P K J
authors.initials: MP
authors.lastname: Engelen
authors.affiliation: Dept. Pediatric Pulmonology, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: G
authors.initials: G
authors.lastname: Com
authors.affiliation: Dept. Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Anderson
authors.affiliation: Center for Translational Research in Aging & Longevity, Dept. Health and Kinesiology, Texas A&M University, College Station, TX, USA; Center for Translational Research in Aging & Longevity, Dept. Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: N E P
authors.initials: NE
authors.lastname: Deutz
mesh_terms: D000293:Adolescent; D000328:Adult; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D001823:Body Composition; D016022:Case-Control Studies; D002648:Child; D002956:Citrulline / Q000097:blood; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D009133:Muscular Atrophy / Q000517:prevention & control; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D011868:Radioisotopes / Q000032:analysis; D053545:Spirulina; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004044:Dietary Proteins; D011868:Radioisotopes; D002956:Citrulline
keywords: Cystic fibrosis; Novel stable isotope method; Pancreatic enzymes; Protein digestibility; Whole-body citrulline production