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Atherosclerosis. 2016 Feb;245:212-21. doi: 10.1016/j.atherosclerosis.2015.11.031. Epub 2015 Dec 17.

The effect of prolonged dietary nitrate supplementation on atherosclerosis development.

Author information

  • 1Department Pathology, CARIM, MUMC, Maastricht, The Netherlands.
  • 2Department Pharmacology, CARIM, Maastricht University, Maastricht, The Netherlands.
  • 3Department Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
  • 4Department Toxicology, Maastricht University, Maastricht, The Netherlands.
  • 5NUTRIM, School for Nutrition, Toxicology and Metabolism, MUMC, Maastricht, The Netherlands.
  • 6Department Surgery/Intensive Care Medicine, MUMC, Maastricht, The Netherlands.
  • 7Department of Clinical Genetics, MUMC, Maastricht, The Netherlands.
  • 8Department Pathology, CARIM, MUMC, Maastricht, The Netherlands; Department Molecular Genetics, CARIM, Maastricht University, Maastricht, The Netherlands; Department Medical Biochemistry, AMC, Amsterdam, The Netherlands.
  • 9Department Pathology, AMC, Amsterdam, The Netherlands.
  • 10Department Pathology, CARIM, MUMC, Maastricht, The Netherlands. Electronic address:



Short term dietary nitrate or nitrite supplementation has nitric oxide (NO)-mediated beneficial effects on blood pressure and inflammation and reduces mitochondrial oxygen consumption, possibly preventing hypoxia. As these processes are implicated in atherogenesis, dietary nitrate was hypothesized to prevent plaque initiation, hypoxia and inflammation.


Study prolonged nitrate supplementation on atherogenesis, hypoxia and inflammation in low density lipoprotein receptor knockout mice (LDLr(-/-)).


LDLr(-/-) mice were administered sodium-nitrate or equimolar sodium-chloride in drinking water alongside a western-type diet for 14 weeks to induce atherosclerosis. Plasma nitrate, nitrite and hemoglobin-bound nitric oxide were measured by chemiluminescence and electron parametric resonance, respectively.


Plasma nitrate levels were elevated after 14 weeks of nitrate supplementation (NaCl: 40.29 ± 2.985, NaNO3: 78.19 ± 6.837, p < 0.0001). However, prolonged dietary nitrate did not affect systemic inflammation, hematopoiesis, erythropoiesis and plasma cholesterol levels, suggesting no severe side effects. Surprisingly, neither blood pressure, nor atherogenesis were altered. Mechanistically, plasma nitrate and nitrite were elevated after two weeks (NaCl: 1.0 ± 0.2114, NaNO3: 3.977 ± 0.7371, p < 0.0001), but decreased over time (6, 10 and 14 weeks). Plasma nitrite levels even reached baseline levels at 14 weeks (NaCl: 0.7188 ± 0.1072, NaNO3: 0.9723 ± 0.1279 p = 0.12). Also hemoglobin-bound NO levels were unaltered after 14 weeks. This compensation was not due to altered eNOS activity or conversion into peroxynitrite and other RNI, suggesting reduced nitrite formation or enhanced nitrate/nitrite clearance.


Prolonged dietary nitrate supplementation resulted in compensation of nitrite and NO levels and did not affect atherogenesis or exert systemic side effects.

Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.


Atherosclerosis; Blood pressure; Hypoxia; Inflammation; Nitrate

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