Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view

Substantial evidences have been accumulated to suggest the positive effect of branched-chain amino acid (BCAA) supplementation or BCAA-rich diets on the regulation of body weight, muscle protein synthesis, glucose homeostasis, aging process, and healthspan extension. Despite these beneficial effects, epidemiological studies have shown that altered BCAA plasma concentrations and BCAA metabolism are present in several metabolic disorders, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). In this review article, we want to give an overview of the current literature on the different effects of BCAAs in health and disease. We also intend to highlight the results showing the most promising therapeutic effects of dietary BCAA supplementation, and discuss how BCAAs can trigger different and even opposite effects, depending on the catabolic or anabolic states of the organisms. Moreover, we will consider the BCAA effects on dysmetabolism, with a mixture of different anabolic and catabolic signals. These peculiar pharmacodynamic properties may partially explain some markedly different effects found in BCAA supplementation studies. To predict accurately these effects, the overall catabolic/anabolic status of patients should be carefully considered. In wider terms, a correct modulation of dysmetabolic disorders would make nutraceutical interventions with BCAAs more effective.