Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (>20 g/d) vs. low-moderate (<20 g/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers.

Endothelial nitric oxide (NO) is fundamental to cardiovascular health. Dietary nitrate and nitrate from endothelial derived NO metabolism provides a significant contribution to the circulating NO pool through the nitrate–nitrite–NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by the oral microbiota. We aimed to assess the effects of antibacterial mouthwash use on markers of nitrate–nitrite–NO metabolism and blood pressure in treated hypertensive men and women. Fifteen treated hypertensive men and women (mean age 65 years) were recruited to a randomized controlled cross-over trial. The effects of 3-day use of antibacterial mouthwash on oral nitrate to nitrite reduction, salivary and plasma nitrate and nitrite, plasma cyclic guanosine monophosphate (cGMP) and systolic and diastolic blood pressure were compared to control (water). Relative to control, 3-day antibacterial mouthwash use resulted in decreased oral nitrate to nitrite reduction (P = 0.02), decreased salivary nitrite (P = 0.01) and increased salivary nitrate (P < 0.001), and there was a trend toward a decrease in plasma nitrite concentration (P = 0.09). Use of antibacterial mouthwash over 3 days also resulted in higher systolic blood pressure (2.3mm Hg; 95% CI: 0.5, 4.0; P = 0.01), but not diastolic blood pressure (P = 0.4) or plasma cGMP (P = 0.7), relative to control. Interruption of the nitrate–nitrite–NO pathway through the use of antibacterial mouthwash was paralleled by a small elevation of systolic blood pressure in treated hypertensive men and women.

Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine–NO-synthase pathway and the recently discovered enterosalivary nitrate–nitrite–NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health; to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate.

Emerging evidence highlights dietary flavonoids and nitrate as candidates that may explain at least part of the cardioprotective effect of a fruit and vegetable diet. Nitric oxide plays a pivotal role in cardiovascular health. Components of a fruit and vegetable diet that are cardioprotective, in part through effects on nitric oxide status, could substantially reduce the cardiovascular risk profile of the general population with increased intake of such a diet. Epidemiological evidence suggests that dietary flavonoids and nitrate have a cardioprotective effect. Clinical trials with flavonoid- and nitrate-rich foods have shown benefits on measures of vascular health. While the molecular mechanisms by which flavonoids and nitrate are cardioprotective are not completely understood, recent evidence suggests both nonspecific and specific effects through nitric oxide pathways. This review presents an overview of nitric oxide and its key role in cardiovascular health and discusses the possible vascular benefits of flavonoids and nitrate, individually and in combination, through effects on nitric oxide status.