The role of leucine in weight loss diets and glucose homeostasis Donald K. Layman and Jamie I. Baum (University of Illinois Urbana-Champaign) The ideal dietary balance of macronutrients for adult health and weight management remains unknown. Most of the debate is focused on the relative merit of carbohydrates (CHO) versus fats with little attention to the importance of dietary protein quantity or quality. Our research has examined use of diets with high protein (1.6 g/kg.d) and low CHO (CHO/protein ratio < 1.5) compared with current recommendations for diets with low protein (0.8 g/kg.d) and high CHO (CHO/protein > 3.5) for changes in body weight and body composition and effects on glucose homeostasis. Presently, needs for dietary proteins are established by the RDAs as the minimum level of protein necessary to maintain nitrogen balance. The RDAs define the primary use of amino acids as substrates for synthesis of body proteins. There is emerging evidence that additional metabolic roles for some amino acids require plasma and intracellular levels above minimum needs for protein synthesis. The branched-chain amino acid (BCAA) leucine is an example of an amino acid with numerous metabolic roles that function in proportion to cellular concentration. Leucine appears to be a unique marker for dietary protein quality and perhaps a key metabolic regulator of muscle protein synthesis and modulator of the insulin signal resulting in sparing of lean body mass during weight loss and stabilizing of blood glucose through stimulation of the glucose-alanine cycle. Ultimately the effects of a higher protein diet are likely derived both from lower carbohydrates resulting in lower post-prandial increases in blood glucose and insulin and from increased protein providing leucine and gluconeogenic substrates. This review focuses on the contributions of leucine and the BCAA to regulation of muscle protein synthesis and glycemic control during weight loss.