Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study

Abstract

Background: Recent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism.

Objectives: The aim of this pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, prediabetic individuals.

Methods: This is a randomized crossover study involving 12 obese individuals with prediabetes. Participants were randomly assigned to receive a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between. At each visit, an oral-glucose-tolerance test (OGTT) was performed. Collected blood samples were used to measure glucose, insulin, and insulin resistance-associated biomarkers.

Results: BCAA supplementation tended to decrease the plasma glucose area under the curve (AUC) measured by the OGTT (AUC percentage change from supplementation baseline, BCAA: -3.3% ± 3%; low-BCAA: 10.0% ± 6%; P = 0.08). However, BCAA supplementation did not affect plasma insulin during OGTT challenge (BCAA: -3.9% ± 8%; low-BCAA: 14.8% ± 10%; P = 0.28). The plasma concentrations of nerve growth factor (BCAA: 4.0 ± 1 pg/mL; low-BCAA: 5.7 ± 1 pg/mL; P = 0.01) and monocyte chemoattractant protein-1 (BCAA: -0.4% ± 9%; low-BCAA: 29.0% ± 18%; P = 0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control. Plasma interleukin 1β was significantly elevated by BCAA supplementation (BCAA: 231.4% ± 187%; low-BCAA: 20.6% ± 33%; P = 0.05). BCAA supplementation did not affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0% ± 12%; low-BCAA: 9.2% ± 11%), valine (BCAA: 9.1% ± 11%; low-BCAA: 12.0% ± 13%), or isoleucine (BCAA: 2.5% ± 11%; low-BCAA: 7.3% ± 11%).

Conclusions: Our data suggest that BCAA supplementation did not impair glucose metabolism in obese, prediabetic subjects. Further studies are needed to confirm the results seen in the present study. This study was registered at clinicaltrials.gov as NCT03715010.

Keywords: OGTT; branched-chain amino acid (BCAA); glucose metabolism; insulin resistance; obesity; prediabetes.

Copyright © American Society for Nutrition 2019.

Figures

FIGURE 1

Screening, enrollment, random assignment, follow-up, and analysis of samples of the study participants. BCAA, branched-chain amino acid.

FIGURE 2

BCAA supplementation tended to improve glucose metabolism in obese, prediabetic subjects. OGTT was performed before and after supplementation of BCAA and low-BCAA interventions in a crossover fashion. (A) Plasma glucose response during OGTT. (B) Plasma insulin response during OGTT. (C) Plasma glucose AUC percentage changes normalized to the supplementation baseline. (D) Plasma insulin AUC percentage changes normalized to the supplementation baseline. Data are mean ± SE (n = 12). P values were derived from repeated-measures ANOVA with the use of a 2-period crossover design with P < 0.05 representing the test for significance. (C) BCAA supplementation tended to decrease the plasma glucose AUC (as percentage change normalized to supplementation baseline) during OGTT (P = 0.08). BCAA, branched-chain amino acid; OGTT, oral-glucose-tolerance test.

FIGURE 3

BCAA supplementation resulted in significantly decreased plasma NGF concentrations. The figure shows the fasting plasma NGF concentration before (baseline) and after (final) BCAA supplementation with BCAA and low-BCAA powder supplements. Data are mean ± SE (n = 12). P values were derived from ANOVA with the use of a 2-period crossover design, P < 0.01. BCAA, branched-chain amino acid; NGF, nerve growth factor.

FIGURE 4

BCAA supplementation resulted in significantly decreased plasma MCP-1 concentrations. The figure shows the fasting plasma MCP-1 concentration before (baseline) and after (final) BCAA supplementation with BCAA and low-BCAA powder supplements. Data are mean ± SE (n = 12). P values were derived from ANOVA with the use of a 2-period crossover design, P < 0.05. BCAA, branched-chain amino acid; MCP-1, monocyte chemoattractant protein-1.

FIGURE 5

BCAA supplementation resulted in significantly increased plasma IL-1β concentrations. The figure shows the fasting plasma IL-1β concentration before (baseline) and after (final) BCAA supplementation with BCAA and low-BCAA powder supplements. Data are mean ± SE (n = 12). P values were derived from ANOVA with the use of a 2-period crossover design, P < 0.05. BCAA, branched-chain amino acid.

FIGURE 6

There were no significant differences in plasma BCAA concentrations after BCAA supplementation. The figure shows the fasting plasma BCAAs (A) leucine, (B) valine, and (C) isoleucine concentrations as percentage change normalized to the supplementation baseline. Data are mean ± SE (n = 12). BCAA, branched-chain amino acid.

FIGURE 7

There were no significant differences on plasma BCKA concentrations after BCAA supplementation. The figure shows the fasting plasma BCKAs (A) KIV, (B) KIC, and (C) KMV concentrations as percentage change normalized to the supplementation baseline. Data are mean ± SE (n = 12). BCAA, branched-chain amino acid; BCKA, branched-chain α-keto acid; KIC, α-ketoisocaproate; KIV, α-ketoisovalerate; KMV, α-keto-methylvalerate.