Abstract

BACKGROUND: Elevated plasma branched-chain amino acid (BCAA) concentrations are associated with a higher risk of type 2 diabetes and cardiovascular diseases. Lifestyle interventions have been proposed as a strategy to manage plasma BCAA concentrations, but evidence of their effectiveness is limited. OBJECTIVES: We investigated the effects of comprehensive lifestyle interventions on plasma BCAA concentrations over 6 mo and associations between changes in body mass index (BMI), physical fitness, and dietary factors and plasma BCAA changes. METHODS: The PREMIER study was a randomized trial of the effects of behavioral lifestyle interventions. The interventions included counseling on diet, exercise, and weight loss ("Established"), a similar intervention with additional guidance to follow Dietary Approaches to Stop Hypertension ("Established plus DASH"), and an Advice-Only control group. We analyzed data from 713 male and female adult participants during the 6-mo intervention period. Data and biospecimens were obtained through the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center repository, and plasma BCAA concentrations were measured using nuclear magnetic resonance spectroscopy. Multiple linear regression was used to assess the association between intervention groups and BCAA concentrations. RESULTS: The Established [-7.19 μmol/L; 95% confidence interval (CI): 17.45, 3.08] and Established plus DASH (-8.70 μmol/L; 95% CI: -18.95, 1.55) interventions were associated with nonsignificant decreases in BCAA concentrations compared with the control group. Changes in BMI were correlated with changes in BCAA concentrations during the trial (partial Pearson r = 0.24, P < 0.001). Although changes in fitness and fiber intake were also significantly correlated with changes in BCAA concentrations, adjustment for BMI attenuated these correlations. Changes in the DASH and healthy plant-based diet indices and BCAA and protein intakes were not significantly correlated with plasma BCAA changes. CONCLUSIONS: Weight loss resulting from lifestyle interventions is associated with reductions in plasma BCAA concentrations. Improvements in fitness and diet composition are not associated with changes in BCAA concentrations independent of weight loss. This trial was registered at clinicaltrials.gov as NCT0000616.