Elevated circulating levels of branched-chain amino acids (BCAAs) in humans are associated with insulin resistance, and muscle BCAA accumulation accompanies the development of insulin resistance during muscle disuse. Conversely, long-term restriction of BCAAs improves insulin sensitivity in obese, insulin resistant rats, and diets characterised by low BCAA content (e.g. vegan diets) are associated with greater insulin sensitivity. Although BCAAs acutely augment insulin secretion, the effect of acute BCAA restriction on insulin sensitivity in humans remains unclear. This study investigated the effect of omitting BCAAs from an amino acid-carbohydrate drink on forearm glucose uptake in healthy young individuals.

Twenty healthy participants were randomly allocated to either a control group (CON: 4/5 M/F; 26±2 yrs; 23.6±1.0 kg·m^-2) or BCAA-omitted group (BCAA-: 5/6 M/F; 24±1 yrs; 23.2±0.4 kg·m^-2). Both groups visited the laboratory on one occasion, during which they consumed a test drink with 0.4 g·kg body mass^-1 total amino acids, 1.1 g·kg body mass^-1 of dextrose, and 2 g cocoa powder. CON contained all amino acids in the ratio found in milk protein (~20% BCAA); the isonitrogenous BCAA- drink contained all amino acids except BCAAs. Repeated arterialised-venous forearm balance measurements were performed in the fasted state and every 20 min for four hours following drink ingestion to determine glucose, insulin concentrations and forearm glucose uptake (calculated as the arterialised–venous glucose difference × brachial artery blood-flow). Data (mean±SEM) were analysed using repeated-measures ANOVA with group and time as factors. Glucose, insulin, and forearm glucose uptake iAUC and time-to-peak values were compared using independent sample t-tests. All subjects gave their informed consent for inclusion prior to participation. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by national ethics committee (Protocol Number: NL82984.028.23).

Arterialised glucose increased from fasted (3.87±0.10 mmol·L⁻¹) to peak values (6.81±0.21 mmol·L⁻¹; P<0.001) at 47±5 min post drink ingestion, with no differences between groups (all P>0.05). There was a significant time effect for serum insulin, which increased from fasted (8±1 mU·L⁻¹) to peak values (125±11 mU·L⁻¹; time effect P<0.05). Despite observed higher arterialised insulin concentrations in CON, no significant group (P=0.238) or interaction (P=0.359) effects were observed. In line, insulin iAUC and time to peak were not different between groups (all P>0.05). Forearm glucose uptake increased by ~5.5-fold from fasted (0.6±0.1 μmol·100 g forearm-mass⁻¹·min⁻¹) to peak (6.1±0.8 μmol·100 g forearm-mass⁻¹·min⁻¹ (P<0.001), at 85±12 min, similarly between groups (P>0.05). Analogously, there was no difference in forearm glucose uptake iAUC over the 4-hour postprandial period between groups (P>0.05).

In conclusion, BCAA omission from an amino acid-carbohydrate drink does not alter acute postprandial arterialised glucose or insulin concentrations, despite observed higher insulin responses in the group that consumed BCAAs. This resulted in similar postprandial forearm glucose uptake between groups. Based on the observed lower insulin response after the BCAA-omitted drink, we speculate that repeated or prolonged exposure, testing under insulin-clamp conditions, and/or application in insulin-resistant populations, may provide insights into BCAA metabolism that are not evident acutely in our population of healthy young individuals.