The role of dietary nitrate in regulation of blood pressure and metabolism

A diet rich in vegetables is recommended for health in general and is also associated with lower blood pressure. Research suggests that inorganic nitrate present in leafy green vegetables could be a contributing factor for the favourable effect. Nitrate from the diet is reduced to nitrite by oral bacteria and further metabolised to nitric oxide (NO) in blood and tissues. The nitrate-nitrite-NO pathway is an alternative way of NO formation in addition to endogenous NO production by the NO synthases. NO is a potent signalling molecule involved in regulation of blood flow and metabolic function. In subjects with pre-hypertension and hypertension (n = 231) the effect on blood pressure after supplementing with nitrate-rich vegetables or potassium nitrate for 5 weeks was compared to low-nitrate vegetables. Also, we examined the handling of nitrate among women and men. Nitrate-rich leafy green vegetables or a nitrate pill did not lower 24 h ambulatory blood pressure in this patient group. However, the renal handling of nitrate seemed to differ between women and men at basal conditions. In another study we investigated if interruption of oral bacterial conversion of nitrate to nitrite could affect metabolic rate in healthy volunteers. In this cross over study, subjects used antiseptic mouthwash or placebo for 3 days followed by measurements of resting metabolic rate. There was no difference in resting metabolic rate after antiseptic mouthwash use. Lastly, the role of an acidic milieu in the gastric lumen for any acute blood pressure effect of nitrite was studied. Healthy men were given a proton pump inhibitor or placebo pills prior to a bolus dose of nitrite. Interestingly, the blood pressure reduction caused by nitrite was blunted by the proton pump inhibitor indicating that a low gastric pH is required for bio-activation of orally administered nitrite. The studies in this thesis address cardiovascular and metabolic effects after supplementing or blocking the nitrate-nitrite-NO pathway. They have generated novel insights about clinical application of dietary nitrate intake, sex differences in nitrate handling and bio-activation of nitrite.

List of scientific papers

I. A randomized clinical trial of the effects of green leafy vegetables and inorganic nitrate on blood pressure. Michaela L Sundqvist, Filip J Larsen, Mattias Carlström, Matteo Bottai, John Pernow, Mai-Lis Hellénius, Eddie Weitzberg* and Jon O Lundberg*. Am J Clin Nutr. 2020;00:1-8. *Shared senior authorship.
https://doi.org/10.1093/ajcn/nqaa024

II. Nitrate and nitrite handling in hypertensive men and women. Michaela L Sundqvist, Mattias Carlström, Jon O Lundberg and Eddie Weitzberg. [Manuscript]

III. Effects of antiseptic mouthwash on resting metabolic rate: A randomized, double blind, cross over study. Michaela L Sundqvist, Jon O Lundberg and Eddie Weitzberg. Nitric Oxide. 2016;61:38-44.
https://doi.org/10.1016/j.niox.2016.10.003

IV. Blood pressure-lowering effects of orally ingested nitrite is abolished by a proton pump inhibitor. Marcelo F Montenegro, Michaela L Sundqvist, Filip J Larsen, Zhengbing Zhuge, Mattias Carlström, Eddie Weitzberg and Jon O Lundberg. Hypertension. 2017;69(1):23-31.
https://doi.org/10.1161/HYPERTENSIONAHA.116.08081