Therapeutic Role of Dietary Nitrates on Cardiorespiratory Function in Cancer Survivors

Abstract

IntroductionThe adverse physiological consequences of anticancer therapy include direct injury to the cardiovascular‐skeletal muscle axis. As such, cancer patients are at an increased risk of both cancer therapy‐related and age‐related pathological outcomes, including primary cardiovascular disease, exercise intolerance, and cancer‐related fatigue. To date, however, therapeutic strategies that mitigate these negative effects within the human body have yet to be established. Previous work has demonstrated that dietary nitrate (NO3−) supplementation can improve cardiac, vascular, and cardiorespiratory exercise parameters, highlighting its potential therapeutic use in clinical populations. Therefore, we hypothesized that NO3− supplementation improves both cardiac performance and exercise capacity. We also investigated the effects of NO3− supplementation on estimates of components of the convective oxygen transport pathway to obtain insight into potential mechanisms of action.MethodsTo date, 5 cancer survivors (58.6 ± 11.3 years) with a history of anticancer therapy completed a randomized, double‐blind, crossover study with an acute, single‐dose administration of NO3− or placebo (PL) [140 mL]. Transthoracic echocardiographic measures at rest were made to obtain left ventricular stroke volume. Patients performed a supine‐cycling steady‐state exercise test (30W) and a maximal‐effort cardiopulmonary exercise test, with measurements of arterial blood pressure, stroke volume, and cardiac output.ResultsThere was a statistically significant increase in plasma nitrite during the NO3− condition compared to PL (NO3− 1300 ± 963 μM vs. PL 111 ± 49 μM, respectively; P = 0.02). Additionally, we observed a decrease in oxygen uptake (VO2) during steady‐state exercise with NO3− compared to PL (NO3− 8.2 ± 2.4 vs. PL 8.6 ± 2.5 ml/kg/min; P = 0.03), indicating an improved exercise efficiency. Resting and steady‐state arterial blood pressure, stroke volume, and cardiac output were not different between conditions. Furthermore, we did not observe any differences between conditions for VO2 peak (NO3− 22.87 ± 4.14 vs. PL 23.45 ± 4.4 ml/kg/min; P = 0.31) or total work done (NO3− 75.73 ± 29.9 vs. PL 75.82 ± 31.3 kJ; P = 0.48) during the maximal‐effort cardiopulmonary exercise test. Similarly, there was no difference is peak cardiac output, convective O2 transport, or the arterial‐venous O2 difference.ConclusionsA single‐dose of inorganic nitrate supplementation in cancer survivors with a history of anticancer therapy enhanced steady‐state exercise efficacy, but had no effect on exercise cardiac performance or peak exercise capacity.