Dietary nitrate, vascular function and inflammation

The risk for cardiovascular diseases (CVD) increases with advancing age. Developing effective lifestyle-based strategies to promote, preserve or restore cardiovascular health with ageing is therefore a high priority. With this clinical research, we investigate the innovative concept that an increased intake of dietary nitrate (through beetroot juice) could be a feasible adjuvant therapy to treat elevated blood pressure and improve blood vessel function in older adults. High blood pressure is another major risk factor for CVD. Inorganic dietary nitrate, found abundantly in beetroot and green leafy vegetables, is a source of nitric oxide (NO), a signalling molecule that is important for cardiovascular health. NO is also produced in the human body, but the bodys production and availability of NO decrease during ageing and CVD. The declined NO availability is associated with impaired blood vessel function, unresolved inflammatory responses, and an increased CVD risk. Dietary nitrate is an additional NO source. Following the intake of nitrate through the diet, NO is produced in a pathway that involves commensal bacteria in the mouth. Dietary nitrate elicits various beneficial physiological effects, but these benefits have mostly been shown in young, healthy individuals. As one of a few studies involving an older population group, the results of our previous study suggested positive short-term effects of nitrate-rich beetroot juice on blood pressure and inflammation markers in healthy older adults. However, little is known about whether dietary nitrate improves cardiovascular health in older populations with high blood pressure. The overall aim of this randomized, placebo-controlled crossover study is to investigate whether the daily intake of nitrate-rich beetroot juice over four weeks translates into improved cardiovascular health-related outcomes in older adults with treated mild high blood pressure. Men and women, between the ages of 55 and 70 years, who have been diagnosed with grade 1 high blood pressure and who are taking two or more blood-pressure lowering medications will be recruited. The study will investigate whether the increased dietary nitrate intake further lowers blood pressure and improves blood vessel function. A specific aim is to examine whether the nitrate intake results in favorable changes in the oral bacteria community and the systemic inflammatory status, and whether these changes correlate with cardiovascular-related outcomes. This research will offer information on the value of dietary nitrate to counteract chronic inflammation, the latter of which plays a role in developing or worsening cardiovascular disorders, such as high blood pressure. Collectively, the expected results of this study will provide important new evidence of whether nitrate-rich beetroot juice could be a key component of therapeutic interventions to improve cardiovascular health in individuals with high blood pressure.

Cardiovascular diseases (CVD) are the primary cause of death in modern societies. Impaired function of blood vessels and high blood pressure (or hypertension) are important reasons why the risk of CVD increases with advancing age. With this clinical research, we evaluated whether previously reported cardiovascular benefits of inorganic nitrate from vegetable sources such as beetroot juice translate into improved vascular function and blood pressure-lowering in older men and women with medically treated hypertension. The results of this randomized, placebo-controlled crossover study suggest that a single dose of 70 milliliters of concentrated beetroot juice containing 400 milligrams of nitrate slightly improved vascular function and blood pressure three hours after the juice intake. Contrary to the acute responses, the daily consumption of 270 milliliters of nitrate-rich beetroot juice (800 milligrams nitrate), compared with nitrate-depleted beetroot juice (placebo), over a period of four weeks, did not sustainably improve vascular function or further lower blood pressure in the 15 participants of our study. As another important finding, subtle favorable changes in some blood biomarkers of oxidative stress and inflammation were observed following the regular intake of nitrate. Furthermore, along with increases in blood and saliva biomarkers of nitrate metabolism and bio-activation, the increased nitrate intake over 4 weeks increased the number of specific commensal bacteria in the mouth that convert nitrate to nitrite. These bacteria play a key role in the conversation of dietary nitrate into nitrite and nitric oxide (NO), a signaling molecule that is central for cardiovascular function and health. Strengths of this research include its robust experimental design and the use of "gold standard"-approaches to assess blood vessel function (forearm blood flow measurements) and blood pressure (24-hour ambulatory blood pressure and home blood pressure). We used stringent study criteria and took thorough measures to control factors known to influence nitrate metabolism and NO signaling. Moreover, we used a combination of contemporary biomarkers and analyzed the microbial community in the mouth to gain insights into possible mechanisms of how the intervention with nitrate may influence the function of the vascular system. Taken together, our findings suggest no major sustained benefits of a relatively high intake of nitrate in the form of beetroot juice on vascular function or blood pressure in this population group. The data from this research, however, point toward subtle improvements in the oxidative stress and systemic inflammatory status by an increased nitrate intake. This offers support for additional mechanisms through which nitrate from plant foods exerts beneficial effects on cardiovascular health. These findings provide new information on the efficacy of nitrate-based interventions for healthy vascular aging and the prevention of CVD. They add important knowledge to an active research area on the physiological and therapeutic effects of food components.