Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials

Am J Clin Nutr. 2016 Feb;103(2):505-11. doi: 10.3945/ajcn.115.117689. Epub 2016 Jan 20.


Background: Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associated with diabetes risk; however, little is known about how a long-term dietary intervention for weight loss affects circulating amino acids.

Objectives: We examined the effects of weight-loss diets on long-term changes in plasma amino acids and the associations of these changes with weight loss and the improvement of insulin resistance.

Design: We repeatedly measured plasma amino acid profiles over 2 y in overweight or obese participants from 2 randomized, dietary intervention, weight-loss trials [774 subjects from the POUNDS LOST (Preventing Overweight Using Novel Dietary Strategies Trial) and 318 subjects from the DIRECT (Dietary Intervention Randomized Controlled Trial)].

Results: Intervention diets consistently lowered most of the amino acid concentrations, including BCAAs and AAAs, in both trials. In the POUNDS LOST, average-protein diets (15% of daily energy) showed stronger effects than did high-protein diets (25% of daily energy) on reducing concentrations of the diabetes-associated BCAA valine at 6 mo independent of the weight change. In both trials, weight loss was directly related to the concurrent reduction of the BCAAs leucine and isoleucine, the AAAs tyrosine and phenylalanine, and 4 other amino acids. For example, per kilogram of weight loss, there was a 0.04-SD decrease in log tyrosine (∼0.6 μmol/L) in both trials. In addition, we showed that reductions in alanine and the AAA tyrosine were significantly related to improved insulin resistance (measured with the use of the homeostasis model assessment of insulin resistance), independent of weight loss, in both trials (both P < 0.05). For example, per 1-SD decrease in log tyrosine (∼17 μmol/L), there was a 0.04-SD (∼3%) improvement in insulin resistance in the POUNDS LOST and a 0.13-SD (∼8%) improvement in insulin resistance in the DIRECT.

Conclusion: Our findings underscore the potential importance of dietary interventions in improving amino acid profiles (i.e., reducing diabetes risk-enhancing amino acid concentrations) along with and beyond weight loss. The POUNDS LOST and the DIRECT were registered at clinicaltrials.gov as NCT00072995 and NCT00160108, respectively.

Keywords: dietary intervention; insulin resistance; metabolomics; plasma amino acids; weight loss.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acids / blood*
  • Amino Acids, Aromatic / blood
  • Amino Acids, Branched-Chain / blood
  • Body Mass Index
  • Boston / epidemiology
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diet, Fat-Restricted* / adverse effects
  • Diet, Reducing* / adverse effects
  • Dietary Proteins / administration & dosage
  • Dietary Proteins / adverse effects
  • Down-Regulation
  • Female
  • Humans
  • Insulin Resistance*
  • Louisiana / epidemiology
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / diet therapy*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Overweight / blood
  • Overweight / diet therapy*
  • Overweight / metabolism
  • Overweight / physiopathology
  • Risk
  • Weight Loss


  • Amino Acids
  • Amino Acids, Aromatic
  • Amino Acids, Branched-Chain
  • Dietary Proteins

Associated data

  • ClinicalTrials.gov/NCT00072995
  • ClinicalTrials.gov/NCT00160108