Whey protein supplementation does not alter plasma branched-chained amino acid profiles but results in unique metabolomics patterns in obese women enrolled in an 8-week weight loss trial

J Nutr. 2015 Apr;145(4):691-700. doi: 10.3945/jn.114.203943. Epub 2015 Feb 4.


Background: It has been suggested that perturbations in branched-chain amino acid (BCAA) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs. Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism, but there is limited evidence in humans.

Objective: We hypothesize that a diet rich in BCAAs will increase BCAA catabolism, which will manifest in a reduction of fasting plasma BCAA concentrations.

Methods: The metabolome of 27 obese women with metabolic syndrome before and after weight loss was investigated to identify changes in BCAA metabolism using GC-time-of-flight mass spectrometry. Subjects were enrolled in an 8-wk weight-loss study including either a 20-g/d whey (whey group, n = 16) or gelatin (gelatin group, n = 11) protein supplement. When matched for total protein by weight, whey protein has 3 times the amount of BCAAs compared with gelatin protein.

Results: Postintervention plasma abundances of Ile (gelatin group: 637 ± 18, quantifier ion peak height ÷ 100; whey group: 744 ± 65), Leu (gelatin group: 1210 ± 33; whey group: 1380 ± 79), and Val (gelatin group: 2080 ± 59; whey group: 2510 ± 230) did not differ between treatment groups. BCAAs were significantly correlated with homeostasis model assessment of insulin resistance at baseline (r = 0.52, 0.43, and 0.49 for Leu, Ile, and Val, respectively; all, P < 0.05), but correlations were no longer significant at postintervention. Pro- and Cys-related pathways were found discriminant of whey protein vs. gelatin protein supplementation in multivariate statistical analyses.

Conclusions: These findings suggest that BCAA metabolism is, at best, only modestly affected at a whey protein supplementation dose of 20 g/d. Furthermore, the loss of an association between postintervention BCAA and homeostasis model assessment suggests that factors associated with calorie restriction or protein intake affect how plasma BCAAs relate to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00739479.

Keywords: BCAA; Cys; Leu; Pro; dairy; metabolic syndrome; metabolomics; obesity; protein; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Amino Acids, Branched-Chain / administration & dosage
  • Amino Acids, Branched-Chain / blood*
  • Blood Glucose
  • Body Mass Index
  • Caloric Restriction
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Dietary Carbohydrates / administration & dosage
  • Dietary Fats / administration & dosage
  • Dietary Proteins / administration & dosage
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gelatin / administration & dosage
  • Homeostasis
  • Humans
  • Insulin / blood
  • Metabolome*
  • Middle Aged
  • Milk Proteins / administration & dosage*
  • Multivariate Analysis
  • Obesity / blood
  • Obesity / diet therapy*
  • Waist Circumference
  • Weight Loss*
  • Whey Proteins


  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Insulin
  • Milk Proteins
  • Whey Proteins
  • Gelatin

Associated data

  • ClinicalTrials.gov/NCT00739479