Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial

Abstract

BACKGROUND: Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3 (-)) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. METHODS AND RESULTS: Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3 (-) in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3 (-). Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3 (-) increased (P<0.05-0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3 (-) intake. Calculated maximal velocity of knee extension was also higher after NO3 (-) ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. CONCLUSIONS: In this pilot study, acute dietary NO3 (-) intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.