The role of inorganic nitrate and nitrite in cardiovascular disease risk factors: a systematic review and meta-analysis of human evidence

Context: Depleted nitric oxide levels in the human body play a major role in cardiovascular disease pathogenesis. Inorganic nitrate/nitrite (rich dietary sources include beetroot and spinach) can act as a nitric oxide donor because nitrate/nitrite can be metabolized to produce nitric oxide. Objective: This review and meta-analysis sought to investigate the role of inorganic nitrate/nitrite in preventing or treating cardiovascular disease risk factors in humans. Data Sources: Electronic databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Scopus, were searched. Data Extraction: Experimental trials examining the effect of oral inorganic nitrate/nitrite intake on cardiovascular disease risk factors were included for systematic analysis. Results: Thirty-four studies were included for qualitative synthesis, 23 of which were eligible for meta-analysis. Included studies measured the following outcomes: blood pressure, endothelial function, arterial stiffness, platelet aggregation, and/or blood lipids. Inorganic nitrate intake was found to significantly reduce resting blood pressure (systolic blood pressure: -4.80 mmHg, P < 0.0001; diastolic blood pressure: -1.74 mmHg, P = 0.001), improve endothelial function (flow-mediated dilatation: 0.59%, P < 0.0001), reduce arterial stiffness (pulse wave velocity: -0.23 m/s, P < 0.0001; augmentation index: -2.1%, P = 0.05), and reduce platelet aggregation by 18.9% (P < 0.0001). Conclusions: Inorganic nitrate consumption represents a simple strategy for targeting cardiovascular disease risk factors. Future studies investigating the long-term effects of inorganic nitrate on cardiovascular disease outcomes are warranted.