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

Abstract

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.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

Heat map of correlations of changes in amino acid concentrations in the Preventing Overweight Using Novel Dietary Strategies Trial. There were 643 participants included in the 6-mo–change analysis (A) and 527 participants in the 2-y–change analysis (B). Axes are lists of amino acids. The color of the square at an intersecting pair of amino acids represents the age-, sex-, and BMI-adjusted pairwise Pearson correlation coefficient between the changes in these amino acid concentrations. At the extremes of the color gradient, which is indicated below the figure, red represents the strongest positive correlation (r = +1) between the changes, and green represents the strongest inverse correlation (r = −1) between the changes; white or no color represents no correlation (r = 0) between the changes. The predominance of red and pink and the absence of green shows that the changes in concentrations of amino acids were generally positively correlated with each other (i.e., as one went up or down, many others changed similarly).

FIGURE 2

Significant associations between changes in weight-loss–related amino acid concentrations and changes in the HOMA-IR. Generalized estimating equations handled the data at 6 mo and 2 y as repeated measurements and put both measurements in the model at the same time. Covariates include age, sex, race (in the POUNDS LOST only), dietary group, baseline BMI, follow-up time, baseline respective amino acid concentration, baseline HOMA-IR, and concurrent weight change. The P value for the association of changes in insulin resistance with changes in alanine was 0.0004 and, with changes in tyrosine, was 0.048 in the POUNDS LOST (n = 774); corresponding P values were 0.011 and 0.030, respectively, in the DIRECT (n = 318). The changes in amino acids and HOMA-IR were in the same direction (i.e., both decreased); therefore, their associations were positive as shown in the figure. DIRECT, Dietary Intervention Randomized Controlled Trial; POUNDS LOST, Preventing Overweight Using Novel Dietary Strategies Trial.