Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness

Metabolism. 2013 Jul;62(7):961-9. doi: 10.1016/j.metabol.2013.01.007. Epub 2013 Feb 1.


Objective: To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI).

Materials/methods: This study was conducted as part of the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) project. Individuals from 3 cohorts were classified as lean (BMI<25kg/m²), overweight (BMI≥25kg/m², BMI<30kg/m²) or obese (BMI≥30kg/m²). Cardiometabolic abnormalities were defined as: (1) impaired fasting glucose (≥100mg/dL and ≤126mg/dL); (2) hypertension; (3) triglycerides ≥150mg/dL; (4) HDL-C <40mg/dL in men, <50mg/dL in women; and (5) insulin resistance (calculated Homeostatic Model Assessment (HOMA-IR) index of >5.13). MW individuals were defined as having <2 cardiometabolic abnormalities and MUW individuals had≥two cardiometabolic abnormalities. Targeted profiling of 55 metabolites used mass-spectroscopy-based methods. Principal components analysis (PCA) was used to reduce the large number of correlated metabolites into clusters of fewer uncorrelated factors.

Results: Of 1872 individuals, 410 were lean, 610 were overweight, and 852 were obese. Of lean individuals, 67% were categorized as MUW, whereas 80% of overweight and 87% of obese individuals were MUW. PCA-derived factors with levels that differed the most between MW and MUW groups were factors 4 (branched chain amino acids [BCAA]) [p<.0001], 8 (various metabolites) [p<.0001], 9 (C4/Ci4, C3, C5 acylcarnitines) [p<.0001] and 10 (amino acids) [p<.0002]. Further, Factor 4, distinguishes MW from MUW individuals independent of BMI.

Conclusion: BCAA and related metabolites are promising biomarkers that may aid in understanding cardiometabolic health independent of BMI category.

Trial registration: NCT00054925.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Amino Acids, Branched-Chain / blood*
  • Amino Acids, Branched-Chain / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Blood Banks
  • Body Mass Index
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Humans
  • Insulin Resistance
  • Male
  • Metabolic Diseases / blood*
  • Metabolic Diseases / complications
  • Metabolic Diseases / metabolism
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / metabolism
  • Metabolomics / methods
  • Middle Aged
  • Obesity / blood*
  • Obesity / complications
  • Obesity / metabolism
  • Overweight / blood*
  • Overweight / complications
  • Overweight / metabolism
  • Principal Component Analysis
  • Thinness / blood*
  • Thinness / complications
  • Thinness / metabolism


  • Amino Acids, Branched-Chain
  • Biomarkers

Associated data