The Effect of Dietary Inorganic Nitrate Supplementation on Cardiac Function during Submaximal Exercise in Men with Heart Failure with Reduced Ejection Fraction (HFrEF): A Pilot Study

Abstract

Heart failure with reduced ejection fraction (HFrEF) is a common end point for patients with coronary artery disease and it is characterized by exercise intolerance due, in part, to a reduction in cardiac output. Nitric oxide (NO) plays a vital role in cardiac function and patients with HFrEF have been identified as having reduced vascular NO. This pilot study aimed to investigate if nitrate supplementation could improve cardiac measures during acute, submaximal exercise. Five male participants (61 ± 3 years) with HFrEF (EF 32 ± 2.2%) completed this pilot study. All participants supplemented with inorganic nitrate (beetroot juice) or a nitrate-depleted placebo for ~13 days prior to testing. Participants completed a three-stage submaximal exercise protocol on a recumbent cycle ergometer with simultaneous echocardiography for calculation of cardiac output (Q), stroke volume (SV), and total peripheral resistance (TPR). Heart rate and blood pressure were measured at rest and during each stage. Both plasma nitrate (mean = ~1028%, p = 0.004) and nitrite (mean = ~109%, p = 0.01) increased following supplementation. There were no differences between interventions at rest, but the percent change in SV and Q from rest to stage two and stage three of exercise was higher following nitrate supplementation (all p > 0.05, ES > 0.8). Both interventions showed decreases in TPR during exercise, but the percent reduction TPR in stages two and three was greater following nitrate supplementation (p = 0.09, ES = 0.98 and p = 0.14, ES = 0.82, respectively). There were clinically relevant increases in cardiac function during exercise following supplementation with nitrate. The findings from this pilot study warrant further investigation in larger clinical trials.

Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies

“…However, as this study was observational, cause-effect relationships cannot be established. Moreover, the findings are at contrast to the beneficial effects of NO 3 − shown in most [152][153][154][155], but not all [156,157], short term intervention trials which show that NO 3 − improves cardiac function and/or exercise capacity in heart failure patients. Clearly, more studies with larger cohorts are required to determine the extent to which genetic variation influences the responsiveness to NO 3 − supplementation, but the findings from these two studies raise the possibility that that genetic factors could contribute towards the inter-individual variability reported by many studies.…”

The Role of Nutrition in the Development and Management of Chronic Obstructive Pulmonary Disease

“…Dietary nitrate supplementation has been shown to have beneficial effects, primarily related to physical performance in both healthy [ 134 ] and disease states [ 3 , 4 , 6 , 135 ], including peripheral artery disease [ 136 ], hypertension [ 137 ], and heart failure [ 137 , 138 , 139 ], although limited information is available with regard to COPD. Nitrate supplementation, primarily through beetroot juice, has been tied to improvements in vascular function [ 140 ] and exercise tolerance [ 136 ], two cardinal features of COPD.…”