Leucine as a pharmaconutrient in health and disease.
ABSTRACT Amino acids do not merely represent precursors for de-novo protein synthesis, but also function as nutritional signals regulating various metabolic processes. In fact, ample evidence has been generated to show that various tissues respond to changes in amino acid availability via signal transduction pathways that are also regulated by hormones such as insulin, glucagon, and insulin-like growth factor 1.
Amino acids, and leucine in particular, can act as strong insulin secretagogues when administered in combination with carbohydrate. Leucine administration can be applied effectively to improve postprandial glycemic control. Furthermore, amino acids have been shown to stimulate mRNA translation, thereby increasing muscle protein synthesis and stimulating net protein accretion in an insulin-independent manner. These anabolic properties of amino acids have been mainly attributed to the essential amino acids, and leucine in particular. In accordance, the recent in-vivo human studies show that leucine ingestion can augment the blunted muscle protein synthetic response to protein or amino acid ingestion in elderly men.
Leucine has been proposed as a promising pharmaconutrient in the prevention and treatment of sarcopenia and/or type 2 diabetes. Though there are numerous applications for the proposed benefits of leucine in health and disease, the recent long-term nutritional intervention studies do not confirm the clinical efficacy of leucine as a pharmaconutrient.
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ABSTRACT: Nutritional supplementation may be used to treat muscle loss with aging (sarcopenia). However, if physical activity does not increase, the elderly tend to compensate for the increased energy delivered by the supplements with reduced food intake, which results in a calorie substitution rather than supplementation. Thus, an effective supplement should stimulate muscle anabolism more efficiently than food or common protein supplements. We have shown that balanced amino acids stimulate muscle protein anabolism in the elderly, but it is unknown whether all amino acids are necessary to achieve this effect. We assessed whether nonessential amino acids are required in a nutritional supplement to stimulate muscle protein anabolism in the elderly. We compared the response of muscle protein metabolism to either 18 g essential amino acids (EAA group: n = 6, age 69 +/- 2 y; +/- SD) or 40 g balanced amino acids (18 g essential amino acids + 22 g nonessential amino acids, BAA group; n = 8, age 71 +/- 2 y) given orally in small boluses every 10 min for 3 h to healthy elderly volunteers. Muscle protein metabolism was measured in the basal state and during amino acid administration via L-[ring-(2)H(5)]phenylalanine infusion, femoral arterial and venous catheterization, and muscle biopsies. Phenylalanine net balance (in nmol x min(-1). 100 mL leg volume(-1)) increased from the basal state (P < 0.01), with no differences between groups (BAA: from -16 +/- 5 to 16 +/- 4; EAA: from -18 +/- 5 to 14 +/- 13) because of an increase (P < 0.01) in muscle protein synthesis and no change in breakdown. Essential amino acids are primarily responsible for the amino acid-induced stimulation of muscle protein anabolism in the elderly.American Journal of Clinical Nutrition 08/2003; 78(2):250-8. · 6.50 Impact Factor
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ABSTRACT: The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover. We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living. Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period. Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P < 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant differences between groups. Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.American Journal of Clinical Nutrition 10/2006; 84(3):623-32. · 6.50 Impact Factor
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ABSTRACT: Muscle contraction during exercise, whether resistive or endurance in nature, has profound affects on muscle protein turnover that can persist for up to 72 h. It is well established that feeding during the postexercise period is required to bring about a positive net protein balance (muscle protein synthesis - muscle protein breakdown). There is mounting evidence that the timing of ingestion and the protein source during recovery independently regulate the protein synthetic response and influence the extent of muscle hypertrophy. Minor differences in muscle protein turnover appear to exist in young men and women; however, with aging there may be more substantial sex-based differences in response to both feeding and resistance exercise. The recognition of anabolic signaling pathways and molecules are also enhancing our understanding of the regulation of protein turnover following exercise perturbations. In this review we summarize the current understanding of muscle protein turnover in response to exercise and feeding and highlight potential sex-based dimorphisms. Furthermore, we examine the underlying anabolic signaling pathways and molecules that regulate these processes.Journal of Applied Physiology 12/2008; 106(5):1692-701. · 3.48 Impact Factor