Supplementation of Glutamine and Fish Oil Versus Placebo in Patients With Heart Failure (GLUTFISH-HF)

The aim of this study is to determine whether supplementation of glutamine and fish oil can improve peripheral skeletal muscle function and metabolism in patients with heart failure. The investigators propose a randomized, double-blind, placebo controlled study comparing the combined supplementation of fish oil and glutamine with placebo in patients with stable heart failure. 30 patients with heart failure will be randomized to either receiving 6.5 g fish oil/d and 8 g glutamine/d (n=15) or placebo (n=15) for 90 days. The primary outcome in this study is the change in muscle functional capacity measured as changes in maximum muscle strength and fatigability, peak VO2 and exercise time after supplementation. A secondary outcome is the measurement of systemic and local markers of inflammation.

Heart Failure, Skeletal Muscle Function, Metabolism, Inflammation, Glutamine, Fish oil, Muscle Function

This is a prospective, randomized double-blind, placebo-controlled study design. 38 subjects will be randomized to two groups (19 patients in each group), one taking active fish oil and glutamine supplementation and the other taking placebo for 90 days.

This is a prospective, randomized double-blind, placebo-controlled study design. 38 subjects will be randomized to two groups (19 patients in each group), one taking active fish oil and glutamine supplementation and the other taking placebo for 90 days.

For isometric contractions, participants contracted against a constant 60-degree angle at the knee (dominant leg) and a constant 30 degree angle at the elbow (dominant arm) for 6 seconds. Participants alternated between flexion and extension, 3 repetitions each with a 30 second rest period between each. Data was collected to determine peak torque to body weight (peak torque (PKTQ)/ body weight (BW)).

For isometric contractions, participants contracted against a constant 60-degree angle at the knee (dominant leg) and a constant 30 degree angle at the elbow (dominant arm) for 6 seconds. Participants alternated between flexion and extension, 3 repetitions each with a 30 second rest period between each. Data was collected to determine peak torque to body weight (peak torque (PKTQ)/ body weight (BW)).

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second.

Inclusion Criteria: age greater than 18 years, left ventricular ejection fraction less than or equal to 35%, stable on standard HF medications, and optimal medical therapy. Exclusion Criteria: major cardiovascular events, procedures in the last 6 months, dementia, presence of cardiovascular diseases that may lead to harm if the patient took part in the study (congenital heart disease, long QT syndrome, hypertrophic cardiomyopathy, active myocarditis).

Shahzad K, Chokshi A, Schulze PC. Supplementation of glutamine and omega-3 polyunsaturated fatty acids as a novel therapeutic intervention targeting metabolic dysfunction and exercise intolerance in patients with heart failure. Curr Clin Pharmacol. 2011 Nov;6(4):288-94. doi: 10.2174/157488411798375958.

Wu C, Kato TS, Ji R, Zizola C, Brunjes DL, Deng Y, Akashi H, Armstrong HF, Kennel PJ, Thomas T, Forman DE, Hall J, Chokshi A, Bartels MN, Mancini D, Seres D, Schulze PC. Supplementation of l-Alanyl-l-Glutamine and Fish Oil Improves Body Composition and Quality of Life in Patients With Chronic Heart Failure. Circ Heart Fail. 2015 Nov;8(6):1077-87. doi: 10.1161/CIRCHEARTFAILURE.115.002073. Epub 2015 Aug 12.