Weight loss and insulin resistance improved by branched-chain amino acids

Weight loss and improvement in insulin resistance naturally go hand in hand, and a study just published in the journal Diabetologia confirms that consumption of branched-chain amino acids (BCAAs) helps both. Isoleucine, leucine and valine are already known to promote muscle growth and repair, influence brain signaling for appetite and metabolic rate, help with burn recovery, and be remedial for autism when it includes genetic mutations in BCAA pathways. The investigators' intent was to discern biomarkers for weight loss and insulin resistance:

"Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss."

They cast a wide net to assay 60 metabolites, including non-essential fatty acids (NEFA), β-hydroxybutyrate, ketones, insulin and glucose at the beginning of their study and after 6 months for 500 subjects who had lost at least 4 kg of weight during Phase I of the Weight Loss Maintenance (WLM) trial. They also calculated the standard metric for insulin resistance, the homeostatic model assessment of insulin resistance (HOMA-IR) and added the change in HOMA-IR with weight loss (∆HOMA-IR)." BCAAs stood out from the pack of metabolites in association with weight loss and improvement in insulin resistance:

"Mean weight loss was 8.67 ± 4.28 kg; mean ∆HOMA-IR was −0.80 ± 1.73. Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR and independently associated with ∆HOMA-IR. ∆HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ∆HOMA-IR. These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ∆HOMA-IR."

Fpr clinicians, this evidence supports the use of BCAAs in case management of weight loss and recovery of insulin sensitivity. The authors conclude:

"A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity."