Christina Wu1, Tomoko S Kato1, Ruiping Ji1, Cynthia Zizola1, Danielle L Brunjes1, Yue Deng1, Hirokazu Akashi1, Hilary F Armstrong1, Peter J Kennel1, Tiffany Thomas1, Daniel E Forman1, Jennifer Hall1, Aalap Chokshi1, Matthew N Bartels1, Donna Mancini1, David Seres1, P Christian Schulze2. 1. From the Division of Cardiology, Department of Medicine (C.W., R.J., C.Z., D.L.B., Y.D., H.F.A., P.J.K., T.T., D.E.F., J.H., A.C., M.N.B., D.M., D.S., P.C.S.) and Division of Cardiothoracic Surgery, Department of Surgery (H.F.A.), Columbia University Medical Center, New York, NY; and Department of Cardiovascular Medicine and Organ Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan (T.S.K.). 2. From the Division of Cardiology, Department of Medicine (C.W., R.J., C.Z., D.L.B., Y.D., H.F.A., P.J.K., T.T., D.E.F., J.H., A.C., M.N.B., D.M., D.S., P.C.S.) and Division of Cardiothoracic Surgery, Department of Surgery (H.F.A.), Columbia University Medical Center, New York, NY; and Department of Cardiovascular Medicine and Organ Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan (T.S.K.). pcs2121@cumc.columbia.edu.
Abstract
BACKGROUND: Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure. These have been linked to a progressive catabolic state, skeletal muscle inflammation, and impaired oxidative metabolism. Previous studies suggest beneficial effects of ω-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance. METHODS AND RESULTS: In a randomized double-blind, placebo-controlled trial, 31 patients with heart failure were randomized to either l-alanyl-l-glutamine (8 g/d) and polyunsaturated fatty acid (6.5 g/d) or placebo (safflower oil and milk powder) for 3 months. Cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, 6-minute walk test, hand grip strength, functional muscle testing, echocardiography, and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up. Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies. No differences in muscle function, echocardiography, 6-minute walk test, or hand grip strength and a nonsignificant increase in peak VO2 in the treatment group were found. Lean body mass increased and quality of life improved in the active treatment group. Molecular analysis revealed no differences in muscle fiber composition, fiber cross-sectional area, gene expression of metabolic marker genes (PGC1α, CPT1, PDK4, and GLUT4), and skeletal muscle oxidative capacity. CONCLUSIONS: The combined supplementation of l-alanyl-l-glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure. These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01534663.
RCT Entities:
BACKGROUND: Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure. These have been linked to a progressive catabolic state, skeletal muscle inflammation, and impaired oxidative metabolism. Previous studies suggest beneficial effects of ω-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance. METHODS AND RESULTS: In a randomized double-blind, placebo-controlled trial, 31 patients with heart failure were randomized to either l-alanyl-l-glutamine (8 g/d) and polyunsaturated fatty acid (6.5 g/d) or placebo (safflower oil and milk powder) for 3 months. Cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, 6-minute walk test, hand grip strength, functional muscle testing, echocardiography, and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up. Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies. No differences in muscle function, echocardiography, 6-minute walk test, or hand grip strength and a nonsignificant increase in peak VO2 in the treatment group were found. Lean body mass increased and quality of life improved in the active treatment group. Molecular analysis revealed no differences in muscle fiber composition, fiber cross-sectional area, gene expression of metabolic marker genes (PGC1α, CPT1, PDK4, and GLUT4), and skeletal muscle oxidative capacity. CONCLUSIONS: The combined supplementation of l-alanyl-l-glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure. These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01534663.
Authors: Wellington Forte Alves; Erika Elisa Aguiar; Sergio Botelho Guimarães; Antonio Ribeiro da Silva Filho; Petrúcia Maria Antero Pinheiro; Gabriel dos Santos Dias Soares; Paulo Roberto Leitão de Vasconcelos Journal: Ann Vasc Surg Date: 2010-04-03 Impact factor: 1.466
Authors: Robin D Clugston; Hongfeng Jiang; Man Xia Lee; Roseann Piantedosi; Jason J Yuen; Rajasekhar Ramakrishnan; Michael J Lewis; Max E Gottesman; Li-Shin Huang; Ira J Goldberg; Paul D Berk; William S Blaner Journal: J Lipid Res Date: 2011-08-19 Impact factor: 5.922
Authors: Savina Nodari; Marco Triggiani; Umberto Campia; Alessandra Manerba; Giuseppe Milesi; Bruno M Cesana; Mihai Gheorghiade; Livio Dei Cas Journal: J Am Coll Cardiol Date: 2011-01-06 Impact factor: 24.094
Authors: Raffay S Khan; Aalap Chokshi; Konstantinos Drosatos; Hongfeng Jiang; Shuiqing Yu; Collette R Harris; P Christian Schulze; Shunichi Homma; William S Blaner; Gerald I Shulman; Li-Shin Huang; Ira J Goldberg Journal: J Cardiovasc Pharmacol Date: 2013-04 Impact factor: 3.105
Authors: K van Norren; D Kegler; J M Argilés; Y Luiking; M Gorselink; A Laviano; K Arts; J Faber; H Jansen; E M van der Beek; A van Helvoort Journal: Br J Cancer Date: 2009-03-10 Impact factor: 7.640
Authors: Elissa Driggin; Laura P Cohen; Dympna Gallagher; Wahida Karmally; Thomas Maddox; Scott L Hummel; Salvatore Carbone; Mathew S Maurer Journal: J Am Coll Cardiol Date: 2022-04-26 Impact factor: 27.203
Authors: Hayley Billingsley; Paula Rodriguez-Miguelez; Marco Giuseppe Del Buono; Antonio Abbate; Carl J Lavie; Salvatore Carbone Journal: Nutrients Date: 2019-11-21 Impact factor: 5.717
Authors: Simon Nichols; Gordon McGregor; Abdallah Al-Mohammad; Ali N Ali; Garry Tew; Alasdair F O'Doherty Journal: Eur J Nutr Date: 2019-10-28 Impact factor: 5.614