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: Protein quality evaluation aims to determine the capacity of food sources and diets to meet protein and indispensable amino acid (IAA) requirements. This study determined whether nitrogen balance was affected and whether dietary IAA were adequately obtained from the ad libitum consumption of diets at three levels of protein from different primary sources for 12 days.Nutrition & metabolism. 01/2014; 11:38.
- Critical Care 11/2014; · 4.93 Impact Factor
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ABSTRACT: Liver transplantation is the definitive therapy for cirrhosis, and malnutrition is the most frequent complication in these patients. Sarcopenia or loss of muscle mass is the major component of malnutrition in cirrhotics and adversely affects their outcome. In addition to the metabolic consequences, functional consequences of sarcopenia include reduced muscle strength and deconditioning. Despite nearly universal occurrence of sarcopenia and its attendant complications, there are no established therapies to prevent or reverse the same. Major reasons for this deficiency include the lack of established standardized definitions or measures to quantify muscle mass, as well as paucity of mechanistic studies or identified molecular targets to develop specific therapeutic interventions. Anthropometric evaluation, bioelectrical impedance analysis, and DEXA scans are relatively imprecise measures of muscle mass, and recent data on imaging measures to determine muscle mass accurately are likely to allow well-defined outcome responses to treatments. Resurgence of interest in the mechanisms of muscle loss in liver disease has been directly related to the rapid advances in the field of muscle biology. Metabolic tracer studies on whole body kinetics have been complemented by direct studies on the skeletal muscle of cirrhotics. Hypermetabolism and anabolic resistance contribute to sarcopenia. Reduced protein synthesis and increased autophagy have been reported in cirrhotic skeletal muscle, while the contribution of the ubiquitin-proteasome pathway is controversial. Increased plasma concentration and skeletal muscle expression of myostatin, a TGFβ superfamily member that causes reduction in muscle mass, have been reported in cirrhosis. Hyperammonemia and TNFα have been reported to increase myostatin expression and may be responsible for sarcopenia in cirrhosis. Nutriceutical interventions with leucine enriched amino acid mixtures, myostatin antagonists and physical activity hold promise as measures to reverse sarcopenia. There is even less data on muscle function and deconditioning in cirrhosis and studies in this area are urgently needed. Even though macronutrient replacement is a major therapeutic goal, micronutrient supplementation, specifically vitamin D, is expected to improve outcomes.Current Treatment Options in Gastroenterology 04/2014;