Dietary nitrate supplementation to enhance exercise capacity in patients with COPD: Evidence from a meta-analysis of randomized controlled trials and a network pharmacological analysis

The potential effects of nitrate in patients with chronic obstructive pulmonary disease (COPD) have attracted increased research interest. However, previous clinical trials have reported inconsistent results, and consecutive meta-analyses have failed to reach a consensus. Since some randomized controlled trials have recently been conducted that can provide more evidence, we performed an updated meta-analysis. A comprehensive literature search was conducted using PubMed, the Cochrane Library, Embase, and Web of Science databases to identify trials that assessed the efficacy and safety of nitrate in patients with COPD. The Revman 5.3 software was used for data analysis. Mean difference (MD) or standardized mean difference (SMD) with 95 % confidence interval (CI) was used as the effect measure, and forest plots were used to display individual and pooled results. Network pharmacology analysis was conducted to investigate the potential mechanisms of nitrate action in COPD. Eleven studies involving 287 patients were included in this meta-analysis. The results indicated that dietary nitrate supplementation increased plasma nitrate and nitrite concentrations and fractional exhaled nitric oxide in patients with COPD. Nitrate improved exercise capacity [SMD = 0.38, 95 % CI = 0.04–0.72] and endothelial function [MD = 9.41, 95 % CI = 5.30–13.52], and relieved dyspnea in patients with COPD. Network pharmacology identified AKT1, IL1B, MAPK3, and CASP3 as key treatment targets. Dietary nitrate supplementation could be used as a potential treatment for patients with COPD, especially to increase their exercise capacity. The underlying mechanisms may be related to AKT1, IL1B, MAPK3, and CASP3. •Dietary nitrate supplementation could enhance the exercise capacity of COPD patients, especially improve the ISWT of COPD patients.•Dietary nitrate could enhance exercise capacity in COPD patients, which might be related to AKT1, IL1B, MAPK3 and CASP3.