Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction

Abstract

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.

Do interindividual differences in cardiac output during submaximal exercise explain differences in exercising muscle oxygenation and ratings of perceived exertion?

“…We observed DStO 2 values ranging from À1% to À7%. This magnitude of change aligns with previous cycling exercise studies (Okushima et al 2015;Hirai et al 2017).…”

Lifestyle Interventions with a Focus on Nutritional Strategies to Increase Cardiorespiratory Fitness in Chronic Obstructive Pulmonary Disease, Heart Failure, Obesity, Sarcopenia, and Frailty

“…Nutrition interventions to improve CRF in HFrEF patients have included micronutrient supplementation [76], amino acids (AA) [77][78][79][80][81], nutrition support supplementation [84], N-3 PUFA [82,83], and dietary nitrates [85,86].…”

“…The authors suggested that this may have been related to inadequate dosing; however, a recent trial of inhaled nitrates without ET also failed to increase peak VO 2 in subjects with HFpEF [93]. Dietary nitrate supplementation has also resulted in mixed effects on CRF in small pilot trials of subjects with HFrEF without ET [85,86]. Currently, the INABLE-Training trial (NCT02713126) is combining higher dosing of oral nitrates with a cardiac rehabilitation (CR) program for 12 weeks in a double-blind, randomized placebo-controlled trial of patients with HFpEF on a primary outcome of peak VO 2 .…”

Cutaneous reactive hyperaemia is unaltered by dietary nitrate supplementation in healthy humans

“…Dietary nitrate supplementation elicits a number of physiological effects, such as increased skeletal muscle blood flow during exercise , decreased blood pressure and improved exercise performance and tolerance (Webb et al ., ,; Kapil et al ., ; Kenjale et al ., ; Lansley et al ., ; Lundberg et al ., ; Cermak et al ., ; Ferguson et al ., , ; Bailey et al ., ; Casey et al ., ; Hirai et al ., ). Our laboratory recently demonstrated nitrate supplementation augments cutaneous vasodilatation to both local heating and whole‐body heating (Keen et al ., ; Levitt et al ., ).…”