Leucine as a pharmaconutrient in health and disease

Article · January 2012with24 Reads
DOI: 10.1097/MCO.0b013e32834d617a · Source: PubMed
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.
    • "However, whey protein contains a greater amount of the BCAAs leucine, isoleucine, and valine than does casein. Of the BCAAs, leucine is thought to be the most potent activator of protein synthesis (Katsanos et al., 2006; van Loon, 2012), although a recent study has shown that high levels of nonleucine BCAAs can induce equivalent protein synthesis when given with a whey protein supplement (Churchward-Venne et al., 2012 ). Casein in turn contains several essential amino acids (EAAs), including histine, methionine, and phenylalanine in a greater amount than whey protein, and also contains a greater amount of the non-EAAs arginine, glutamic acid, proline, serine, and tyrosine (Hall et al., 2003). "
    [Show abstract] [Hide abstract] ABSTRACT: Cow’s milk proteins and related bioactive peptides are purported to have a wide range of effects on human health across the life span. Casein and whey protein have both been proposed to play a role in the prevention of chronic age-related conditions such as adverse metabolic health and type 2 diabetes, muscle wasting and sarcopenia, atherosclerosis, hypertension and cardiovascular disease risk, as well as bone health and osteoporosis. Epidemiological studies have shown regular dairy consumption to be associated with decreased prevalence of cardiometabolic risk, an outcome of improved metabolic health, while intervention studies have shown milk proteins to promote postprandial insulin secretion and glycemic control, and under some conditions improve postprandial lipemia and hypertension. The branched-chain amino acids of dairy protein also promote muscle anabolism, important for the maintenance of muscle mass and mobility during aging and, in our current epidemic of obesity, for the maintenance of lean body mass during energy restriction and weight loss. Dietary protein is known to suppress satiety and food intake, and if consumed from a dairy source may support preferential loss of fat rather than lean mass during weight loss. Milk proteins may also be beneficial for bone health during aging. In addition, milk proteins are important for maternal and infant nutrition, with protein playing a major role in growth and development during early life. While public health recommendations for breastfeeding underpin nutrition in young infants, commercial infant formulas are required for mothers unable to breastfeed long term, and formulas containing cow’s milk protein aim to optimize infant health. In this chapter we review the evidence for the potential health benefits of milk proteins, based on human clinical trials, with a particular focus on metabolic health.
    Full-text · Chapter · Dec 2014 · Nutrition & Metabolism
    • "Leucine and insulin share common pathways for activating protein synthesis, suggesting that signal transduction is impaired somewhere within the mammalian target of rapamycin pathway. However, there may be differences in the acute and prolonged effects of leucine supplementation [48]. Research into the role of leucine in different clinical settings has potential implications for the treatment of muscle loss in metabolically stressed patients. "
    [Show abstract] [Hide abstract] ABSTRACT: Proteins and amino acids are widely considered to be subcomponents in nutritional support. However, proteins and amino acids are fundamental to recovery and survival, not only for their ability to preserve active tissue (protein) mass but also for a variety of other functions. Understanding the optimal amount of protein intake during nutritional support is therefore fundamental to appropriate clinical care. Although the body adapts in some ways to starvation, metabolic stress in patients causes increased protein turnover and loss of lean body mass. In this review, we present the growing scientific evidence showing the importance of protein and amino acid provision in nutritional support and their impact on preservation of muscle mass and patient outcomes. Studies identifying optimal dosing for proteins and amino acids are not currently available. We discuss the challenges physicians face in administering the optimal amount of protein and amino acids. We present protein-related nutrition concepts, including adaptation to starvation and stress, anabolic resistance, and potential adverse effects of amino acid provision. We describe the methods for assessment of protein status, and outcomes related to protein nutritional support for critically ill patients. The identification of a protein target for individual critically ill patients is crucial for outcomes, particularly for specific subpopulations, such as obese and older patients. Additional research is urgently needed to address these issues.
    Full-text · Article · Nov 2014
    • "Since the subjects in this study were healthy, one of these roles may be the stimulation of muscle protein synthesis. The relative high abundance of leucine in whey with α-lactalbumin protein may be beneficial to stimulate muscle protein synthesis [46]. The DIAAS can be applied in practice to examine protein quality of food products or mixed diets. "
    [Show abstract] [Hide abstract] ABSTRACT: BackgroundProtein 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.MethodsTwo 12-day randomized crossover design trials were conducted in healthy subjects [n = 70/67 (M/F); age: 19-70 y; BMI: 18.2-38.7 kg/m2]. The relative dietary protein content was lower than [5% of energy (En%)], similar to (15En%), and higher than (30En%) customary diets. These diets had a limited variety of protein sources, containing wheat protein as a single protein source (5En%-protein diet) or 5En% from wheat protein with 10En% (15En%-protein diets) or 25En% (30En%-protein diets) added from whey with α-lactalbumin, soy or beef protein.ResultsThere was a dose-dependent increase in nitrogen excretion with increasing dietary protein content, irrespective of the protein sources (P = 0.001). Nitrogen balance was maintained on the 5En%-protein diet, and was positive on the 15En%- and 30En%-protein diets (P < 0.001) over 12 days. Protein intake from the 5En%-protein diet did not reach the amount necessary to meet the calculated minimal IAA requirements, but IAA were sufficiently obtained from the 15En%- and 30En%-protein diets. In the 15En%- and 30En%-protein conditions, a higher protein intake from the soy-containing diets than from the whey with α-lactalbumin or beef containing diets was needed to meet the minimal IAA requirements.ConclusionProtein intake did not compensate for an insufficient indispensable amino acid intake with a low-protein diet for 12 days.Trial registrationThese trials were registered at clinicaltrials.gov as NCT01320189 and NCT01646749.
    Full-text · Article · Aug 2014
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