Effects of Leucine Supplementation in Combination with Resistance Training and Optimal Dietary Protein Intake in Pre-frail and Frail Older Women

Download or read book Effects of Leucine Supplementation in Combination with Resistance Training and Optimal Dietary Protein Intake in Pre-frail and Frail Older Women written by Kathryn Jacob and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Background: Frailty is a clinical condition associated with loss of muscle mass and strength, whose loss is termed sarcopenia, of which age-related resistance to anabolic stimuli is considered a key factor. Age-related anabolic resistance can be mitigated by a higher protein intake than presently recommended for the general population and has lower insulin sensitivity (IS) as a contributing factor, while mitochondria are centrally implicated in frailty and sarcopenia. Resistance training (RT) is the strongest stimuli to counteract sarcopenia via increasing muscle protein synthesis in the presence of sufficient amino acids, and may also stimulate mitochondrial biogenesis, as well as improve IS in frail older women. Leucine is a unique amino acid that acutely increases muscle protein synthesis independent of insulin. Leucine has paradoxically been shown to have both potential therapeutic value while also being implicated in the pathological development of insulin resistance. Furthermore, leucine has recently been shown to increase mitochondrial biogenesis in myocytes. The effects of chronic leucine supplementation in conjunction with RT on these factors within the context of frailty are currently unknown. Objective: The purpose of this double-blinded placebo-controlled study is to determine the effects of leucine supplementation and RT on indices of anabolism, insulin sensitivity, and mitochondria function in pre-frail and frail older women consuming optimal protein intake. Methodology: Nineteen pre-frail and frail elderly women (77.5 ± 1.3 y), based on the Frailty Phenotype, underwent 3-months of RT 3x/week with protein-optimized diet (~1.2 g·kg BW−1d·−1) and were randomized to 7.5 g/d of leucine supplementation or an isonitrogenous quantity of placebo (alanine). Indices of 1) insulin sensitivity during a metabolic test meal; 2) mitochondrial content (VDAC protein), function (respiration and reactive oxygen species production), and sensitivity to apoptosis (calcium retention capacity and time to mitochondria permeability transition pore opening) in permeabilized muscle fibers; and 3) muscle protein synthesis determined using L-[ring-2H5]phenylalanine infusion in the postabsorptive and postprandial states, muscle fiber profile by immunohistochemistry, body composition by Dual X-ray Absorptiometry, physical function tests and maximal isometric strength were measured pre- and post-intervention. Results: Our main findings were that compared to 12 weeks of RT in pre-frail and frail older women consuming an optimal protein intake, additional leucine supplementation had: 1) no detrimental nor beneficial effect on insulin sensitivity; 2) increased mitochondrial content without affecting mitochondria function, capacity, or sensitivity to apoptosis; and 3) no added benefit on improvements in muscle protein synthesis, muscle function, and Frailty Phenotype. Conclusion: Leucine supplementation does not appear to influence insulin sensitivity, and although leucine increased mitochondrial content, this occurred without associated improvements in mitochondria function in older women consuming an optimal protein intake and undertaking RT in the context of frailty. The RT and dietary protein intake as described in this study appear to effectively and meaningfully stimulate basal (postabsorptive) muscle protein synthesis translating into measurable gains in muscle protein accretion, strength, and function resulting in marked improvements in the Frailty Phenotype." --