Dietary supplements and aging muscle: specific amino acids to combat sarcopenia

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DESCRIPTION (provided by applicant): Sarcopenia, the decline in muscle mass and strength with aging, is multifactorial, due partly to the decreased response of skeletal muscle to dietary protein as well as increased pro-inflammatory cytokines. Oral intake of particular amino acids shows promise to counteract muscle loss in older adults. Specifically, leucine acutely stimulates protein synthesis via mTOR cell signaling pathways, whereas glutamine (Gin), a precursor to other amino acids and glutathione, may decrease inflammation. Arginine (Arg) may further modulate inflammation, regulate mTOR pathways, and increase availability of amino acids to muscle by stimulating insulin secretion and vasodilation. Argine also stimulates secretion of other anabolic hormones and acts as a precursor for protein synthesis. The dietary supplement Juven (Ross Laboratories) is comprised of beta-hydroxy-beta-methylbutyrate (HMB), an active metabolite of leucine, glutamine, and arginine. Whether Juven can improve muscle mass, quality, and function in older adults is unknown. The Specific Aims of this randomized, double-blind, placebo-controlled intervention are to test the hypotheses that, among older adults, Juven versus placebo chronically 1) results in maintenance or gains in appendicular skeletal muscle mass, muscle volume, and physical function; 2) positively affects quality of life; and 3) decreases serum biomarkers of inflammation. Community-dwelling men and women, ages >64 years will be randomized to receive either two doses of Juven (3 g HMB, 14g Gin, 14g Arg) or an isonitrogenous placebo (alanine, glutamic acid, glycine, serine) daily for 6 months. At baseline, 3 months, and 6 months, measurements will include 1) comprehensive body composition evaluation by the gold-standard four-compartment model; 2)appendicular skeletal mass by dual energy X-ray absorptiometry; 3) skeletal muscle volume by magnetic resonance imaging; 4) physical function by a tDattery of physical performance tests; and 5) quality of life by validated questionnaire and the SEIQoL-DW, an assessment tool that allows individuals to define domains of "quality of life" for themselves. PUBLIC HEALTH RELEVANCE: This intervention holistically links physiological outcomes (muscle mass, muscle volume, pro- inflammatory biomarkers) to psychological outcomes (quality of life) and practical physical function measures. No effective means exist to prevent or reverse sarcopenia. As the American population ages, practical, effective interventions will be critical. This clinical research will contribute to an evidence base for dietary supplements that shows potential to enhance muscle metabolism in older adults.