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

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