A Randomized Clinical Trial on Dietary Nitrate and Blood Pressure

Background: Elevated blood pressure (BP) is a major risk factor for cardiovascular disease and premature death worldwide. Hypertension (i.e. BP of ≥140/90 mmHg) is even considered the leading risk factor for global burden of disease. Dietary strategies preventing hypertension includes the Dietary Approaches to Stop Hypertension eating plan. A vegetarian diet and high vegetable intake has also shown beneficial effects on BP regulation. In the last 10 years there is an emerging interest in the positive effects of dietary nitrate (NO3 - ). Inorganic nitrate is converted to nitric oxide (NO) in our body with vasodilatory effects. Vegetables alone contribute with 60-80% (60-80 of 100) of the total nitrate intake in humans and the highest concentrations of this anion are found in green leafy vegetables and beetroots. Several short term studies have shown that administration of nitrate salts or high nitrate vegetables (HNV) have BP lowering effects. A large scale randomized clinical trial is needed to explore long term effects on BP after daily intake of HNV. Methods: The Di etary Ni tric O xide (DINO) study is a single site, randomized clinical trial including subjects (n = 300) between 50-70y with SBP 130-159 mm Hg. A wash out period of 2 weeks is followed by randomization to one of three intervention groups: HNV containing 300 mg nitrate + placebo pill, low nitrate vegetables (LNV) + nitrate supplement (300mg potassium nitrate) or LNV + a placebo pill. All subjects will have a constant vegetable intake during 5 weeks of HNV or LNV provided weekly by the investigators, to consume together with their normal diet. After the wash out period and in the last week of the study 24h ambulatory BP, 24h urine collection, and blood- and saliva samples are taken. Lifestyle habits are also monitored during the study. The primary endpoint is systolic ambulatory BP with 85% (85 of 100) power to detect a difference of 2mm Hg between the groups. Conclusion: The DINO study is designed to investigate the potential contribution of inorganic nitrate to the BP lowering effect attributed to vegetables. In addition, the three armed design makes it possible to evaluate natural sources of nitrate compared to supplements.