Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure

Abstract

Background Skeletal muscle strength, velocity, and power are markedly reduced in heart failure (HF) patients, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially due to 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 HF due to systolic dysfunction. Methods and Results Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in nine HF patients. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35–50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the two highest movement velocities tested (i.e., 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (i.e., 4.74±0.41 vs. 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher following NO3− ingestion (i.e., 12.48±0.95 vs. 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 HF. 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.

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

“…Put in context of reports of increased functional capacity with administration of various other forms of nitrite (intravenous sodium nitrite and inorganic nitrate, which is in beet juice and is converted to nitrite by oral commensal bacteria) (26,27), this report adds to our knowledge base of the physiologic effects of exogenous administration of nitrite in PH due to left heart disease, lung disease, and PAH. Our data provide further evidence that inhaled nitrite lowers left-and right-sided filling pressures in patients with heart failure with preserved ejection fraction.…”

Dietary nitrate increases exercise tolerance in patients with non-ischemic, dilated cardiomyopathy—a double-blind, randomized, placebo-controlled, crossover trial

“…It is probable that differences in baseline fitness/NO bioavailability, medications and NIDCM severity contribute to this variation. Nevertheless, 10 of 11 subjects had increased ISWT distance post-NO 3 -. Exercise capacity is regarded as a principal variable for the evaluation of new therapeutic approaches in NIDCM.…”

“…Thus, 11 subjects completed the study ( T1 Table 1). After NO 3 -consumption, mean ISWT distance increased by 65 Ϯ 41 meters (431 to 496 meters, 15%), whereas there was a decrease of 5 Ϯ 35 meters (437 to 433 meters, 1%) after PL (p ¼ 0.0056). The mean and individual ISWT distances after NO 3 -and PL are shown in…”

“…Ten of the 11 subjects walked further after NO 3 -(30 to 140 meters), whereas 1 had a decreased exercise capacity (-10 meters). However, after PL, only 4 subjects had increased walking capacity (10 to 80 meters), but 7 walked shorter distances (-10 to -60 meters).…”

“…A second, NO synthase-independent pathway has recently been discovered and was found to be involved in simple reduction of dietary, inorganic nitrate to nitrite and NO. 2,3 Acute nitrate consumption has been shown to increase blood nitrate/nitrite levels and exercise performance in healthy, athletic, pulmonary vascular disease (PVD), 4 chronic obstructive pulmonary disease (COPD) 5 and heart failure (HF) subjects. 2 We hypothesized that dietary nitrate supplementation could acutely improve exercise capacity in NIDCM.…”