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Effects of dietary nitrate on blood pressure in healthy volunteers
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.ORCID iD: 0000-0002-1343-8656
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.ORCID iD: 0000-0002-4030-5437
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
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2006 (English)In: New England Journal of Medicine, ISSN 0028-4793, Vol. 28, no 355(26), 2792-3 p.Article in journal (Refereed) Published
Abstract [en]

To the Editor:

Nitric oxide, generated by nitric oxide synthase, is a key regulator of vascular integrity. This system is dysfunctional in many cardiovascular disorders, including hypertension. A fundamentally different pathway for the generation of nitric oxide was recently described in which the anions nitrate (NO3 ) and nitrite (NO2 ) are converted into nitric oxide and other bioactive nitrogen oxides.1-3 Nitrate is abundant in our diet, and particularly high levels are found in many vegetables.3

We examined the effect of 3-day dietary supplementation with either sodium nitrate (at a dose of 0.1 mmol per kilogram of body weight per day) or placebo (sodium chloride, at a dose of 0.1 mmol per kilogram per day) on blood pressure in 17 physically active, healthy volunteers, none of whom smoked (15 men and 2 women; mean age, 24 years). The study had a randomized, double-blind, crossover design with two different treatment periods during which the subjects received either nitrate or placebo; the treatment periods were separated by a washout period of at least 10 days. The compounds were dissolved in water and could not be distinguished by taste or appearance. During the two treatment periods, the subjects were instructed to avoid all foods with a moderate or high nitrate content.3

Systolic blood pressure Effects of 3-Day Dietary Supplementation with Inorganic Nitrate or Placebo on Systolic (Panel A) and Diastolic (Panel B) Blood Pressure in 17 Healthy Volunteers.) and pulse rate did not change significantly after nitrate supplementation, as compared with placebo supplementation. However, the diastolic blood pressure was on average 3.7 mm Hg lower after nitrate supplementation than after placebo supplementation (P<0.02) (Figure 1B), and the mean arterial pressure was 3.2 mm Hg lower (P<0.03). Plasma nitrate levels were higher after nitrate ingestion than after placebo ingestion (mean [±SD], 178±51 and 26±11 μM, respectively; P<0.001), as were plasma nitrite levels (219±105 and 138±38 nM, respectively; P<0.01).

The daily nitrate dose used in the study corresponds to the amount normally found in 150 to 250 g of a nitrate-rich vegetable such as spinach, beetroot, or lettuce. It is clear from earlier studies, such as the Dietary Approaches to Stop Hypertension (DASH) trial, that a diet rich in fruits and vegetables can reduce blood pressure,4,5 but attempts to modify single nutrients have been inconsistent. Therefore, it has been argued that the effect of any individual nutrient is too small to detect in trials. In our study, reduced blood pressure was associated with nitrate supplementation alone; this effect was evident in young normotensive subjects. In fact, it was similar to that seen in the healthy control group in the DASH study.4 The exact mechanism behind the blood-pressure–lowering effect of nitrate needs to be clarified in future studies.

We conclude that short-term dietary supplementation with inorganic nitrate reduces diastolic blood pressure in healthy young volunteers.

Place, publisher, year, edition, pages
2006. Vol. 28, no 355(26), 2792-3 p.
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-303DOI: 10.1056/NEJMc062800PubMedID: 17192551OAI: oai:DiVA.org:gih-303DiVA: diva2:663
Available from: 2007-10-12 Created: 2007-10-12 Last updated: 2017-03-31Bibliographically approved
In thesis
1. Dietary inorganic nitrate: role in exercise physiology, cardiovascular and metabolic regulation
Open this publication in new window or tab >>Dietary inorganic nitrate: role in exercise physiology, cardiovascular and metabolic regulation
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nitric oxide (NO) is a ubiquitous signaling molecule with a vast number of tasks in the body, including regulation of cardiovascular and metabolic function. A decreased bioavailability of NO is a central event in disorders such as hypertension and metabolic syndrome. NO is also important in the regulation of blood flow and metabolism during exercise. The production of NO has previously been thought to be under the exclusive control of the nitric oxide synthases (NOS) but this view is now being seriously challenged. Recent lines of research suggest the existence of an NO-synthase independent pathway in which the supposedly inert NO oxidation products nitrate (NO3-) and nitrite (NO2-) can be reduced back to NO in blood and tissues. An important additional source of nitrate is our everyday diet and certain vegetables are particularly rich in this anion. In this thesis the possibility that dietary derived nitrate is metabolized in vivo to form reactive nitrogen oxides with NO-like bioactivity has been explored. It is shown that nitrate in amounts easily achieved via the diet, increases the systemic levels of nitrite and reduces blood pressure in healthy humans. Moreover, nitrate reduces whole body oxygen cost during submaximal and maximal exercise; a surprising effect involving improvement in mitochondrial efficiency and reduced expression of specific mitochondrial proteins regulating proton conductance. Alterations in the mitochondrial affinity for oxygen can explain this reduction in both submaximal and maximal oxygen consumption and predicts basal metabolic rate in humans. Finally, in mice lacking endothelial NO synthase, dietary supplementation with nitrate could reverse several features of the metabolic syndrome that develop in these animals. These studies demonstrate that dietary nitrate can fuel a nitrate-nitrite-NO pathway with important implications for cardiovascular and metabolic functions in health and disease.

Place, publisher, year, edition, pages
Solna: Karolinska Institutet, 2011
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-2079 (URN)978-91-7457-397-8 (ISBN)
Public defence
2011-06-17, Aulan Farmakologen, Nanna Svartz väg 2, Solna, 09:00 (English)
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Note
Avhandling vid Karolinska Institutet och Gymnastik- och idrottshögskolan, GIHAvailable from: 2012-01-09 Created: 2012-01-09 Last updated: 2016-08-08Bibliographically approved

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