Skip to main content Accessibility help

Dietary nitrate consumption and risk of CHD in women from the Nurses’ Health Study

  • Jacklyn K. Jackson (a1), Geng Zong (a2), Lesley K. MacDonald-Wicks (a1), Amanda J. Patterson (a1), Walter C. Willett (a2) (a3) (a4), Eric B. Rimm (a2) (a3) (a4), JoAnn E. Manson (a3) (a5) and Mark A. McEvoy (a6)...

The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.

Corresponding author
*Corresponding author: M. A. McEvoy, email
Hide All
1. Coulter, SA (2011) Epidemiology of cardiovascular disease in women: risk, advances, and alarms. Tex Heart Inst J 38, 145147.
2. Garcia, M, Mulvagh, SL, Bairey Merz, CN, et al. (2016) Cardiovascular disease in women: clinical perspectives. Circ Res 118, 12731293.
3. Pagidipati, NJ & Peterson, ED (2016) Acute coronary syndromes in women and men. Nat Rev Cardiol 13, 471480.
4. Benziger, CP, Roth, GA & Moran, AE (2016) The global burden of disease study and the preventable burden of NCD. Glob Heart 11, 393397.
5. He, F, Nowson, C, Lucas, M, et al. (2007) Increased consumption of fruit and vegetables is related to a reduced risk of coronary heart disease: meta-analysis of cohort studies. J Hum Hypertens 21, 717728.
6. Bhupathiraju, SN, Wedick, NM, Pan, A, et al. (2013) Quantity and variety in fruit and vegetable intake and risk of coronary heart disease. Am J Clin Nutr 98, 15141523.
7. Lidder, S & Webb, AJ (2013) Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate–nitrite–nitric oxide pathway. Br J Clin Pharmacol 75, 677696.
8. Sindelar, JJ & Milkowski, AL (2012) Human safety controversies surrounding nitrate and nitrite in the diet. Nitric Oxide 26, 259266.
9. Lundberg, JO, Weitzberg, E & Gladwin, MT (2008) The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7, 156167.
10. Moncada, S & Higgs, E (2006) Nitric Oxide and the Vascular Endothelium. The Vascular Endothelium I, pp. 213–254. New York: Springer.
11. Kleinbongard, P, Dejam, A, Lauer, T, et al. (2006) Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 40, 295302.
12. Landmesser, U & Drexler, H (2007) Endothelial function and hypertension. Curr Opin Cardiol 22, 316320.
13. Li, H & Förstermann, U (2000) Nitric oxide in the pathogenesis of vascular disease. J Pathol 190, 244254.
14. Strijdom, H, Chamane, N & Lochner, A (2009) Nitric oxide in the cardiovascular system: a simple molecule with complex actions: review article. Cardiovasc J Afr 20, 303310.
15. Napoli, C & Ignarro, LJ (2009) Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases. Arch Pharm Res 32, 11031108.
16. De Backer, G, Ambrosioni, E, Borch-Johnsen, K, et al. (2003) European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur Heart J 24, 16011610.
17. Mosca, L, Banka, CL, Benjamin, EJ, et al. (2007) Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol 49, 12301250.
18. Kapil, V, Khambata, RS, Robertson, A, et al. (2015) Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension 65, 320327.
19. Jackson, JK, Patterson, AJ, MacDonald-Wicks, LK, et al. (2018) The role of inorganic nitrate and nitrite in cardiovascular disease risk factors: a systematic review and meta-analysis of human evidence. Nutr Rev 76, 348371.
20. MacMahon, S, Peto, R, Collins, R, et al. (1990) Blood pressure, stroke, and coronary heart disease: part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335, 765774.
21. Blekkenhorst, LC, Bondonno, CP, Lewis, JR, et al. (2017) Association of dietary nitrate with atherosclerotic vascular disease mortality: a prospective cohort study of older adult women. Am J Clin Nutr 106, 207216.
22. Liu, AH, Bondonno, CP, Russell, J, et al. (2018) Relationship of dietary nitrate intake from vegetables with cardiovascular disease mortality: a prospective study in a cohort of older Australians. Eur J Nutr (epublication ahead of print version 20 September 2018).
23. Belanger, CF, Hennekens, CH, Rosner, B, et al. (1978) The Nurses’ Health Study. Am J Nurs 78, 10391040.
24. Colditz, GA, Manson, JE & Hankinson, SE (1997) The Nurses’ Health Study: 20-year contribution to the understanding of health among women. J Womens Health (Larchmt) 6, 4962.
25. Salvini, S, Hunter, DJ, Sampson, L, et al. (1989) Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 18, 858867.
26. Willett, WC, Sampson, L, Browne, ML, et al. (1988) The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol 127, 188199.
27. Willett, WC, Sampson, L, Stampfer, MJ, et al. (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122, 5165.
28. Yuan, C, Spiegelman, D, Rimm, EB, et al. (2017) Relative validity of nutrient intakes assessed by questionnaire, 24-hour recalls, and diet records compared with urinary recovery and plasma concentration biomarkers: findings for women. Am J Epidemiol 187, 10511063.
29. US Department of Agriculture, Agriculture Research Service, Nutrient Data Laboratory (2015) USDA nutrient database for standard reference, release 28. (accessed December 2015).
30. Blekkenhorst, LC, Prince, RL, Ward, NC, et al. (2017) Development of a reference database for assessing dietary nitrate in vegetables. Mol Nutr Food Res 61, 1600982.
31. Pannala, AS, Mani, AR, Spencer, JP, et al. (2003) The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans. Free Radic Biol Med 34, 576584.
32. Lajous, M & Willett, WC (2017) Nutritional epidemiology of nitrogen oxides: what do the numbers mean? In Nitrite and Nitrate in Human Health and Disease, pp. 99–109 [NS Bryan and J Loscalzo, editors]. New York: Springer.
33. Hu, FB, Stampfer, MJ, Manson, JE, et al. (1997) Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 337, 14911499.
34. Chiuve, SE, Fung, TT, Rimm, EB, et al. (2012) Alternative dietary indices both strongly predict risk of chronic disease. J Nutr 142, 10091018.
35. Jager, K, Zoccali, C, Macleod, A, et al. (2008) Confounding: what it is and how to deal with it. Kidney Int 73, 256260.
36. Wolf, AM, Hunter, DJ, Colditz, GA, et al. (1994) Reproducibility and validity of a self-administered physical activity questionnaire. Int J Epidemiol 23, 991999.
37. Rimm, EB, Stampfer, MJ, Colditz, GA, et al. (1990) Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1, 466473.
38. Threapleton, DE, Greenwood, DC, Evans, CE, et al. (2013) Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 347, f6879.
39. Rimm, EB, Willett, WC, Hu, FB, et al. (1998) Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 279, 359364.
40. D’Elia, L, Barba, G, Cappuccio, FP, et al. (2011) Potassium intake, stroke, and cardiovascular disease: a meta-analysis of prospective studies. J Am Coll Cardiol 57, 12101219.
41. Bondonno, CP, Blekkenhorst, LC, Prince, RL, et al. (2017) Association of vegetable nitrate intake with carotid atherosclerosis and ischemic cerebrovascular disease in older women. Stroke 48, 17241729.
42. Kang, JH, Willett, WC, Rosner, BA, et al. (2016) Association of dietary nitrate intake with primary open-angle glaucoma: a prospective analysis from the nurses’ health study and health professionals follow-up study. JAMA Ophthalmol 134, 294303.
43. Jackson, JK, Patterson, AJ, MacDonald-Wicks, LK, et al. (2018) Dietary nitrate and diet quality: an examination of changing dietary intakes within a representative sample of Australian women. Nutrients 10, E1005.
44. Dewhurst-Trigg, R, Yeates, T, Blackwell, JR, et al. (2018) Lowering of blood pressure after nitrate-rich vegetable consumption is abolished with the co-ingestion of thiocyanate-rich vegetables in healthy normotensive males. Nitric Oxide 74, 3946.
45. Nadtochiy, SM & Redman, EK (2011) Mediterranean diet and cardioprotection: the role of nitrite, polyunsaturated fatty acids, and polyphenols. Nutrition 27, 733744.
46. Jackson, J, Patterson, AJ, MacDonald-Wicks, L, et al. (2017) The role of inorganic nitrate and nitrite in CVD. Nutr Res Rev 30, 247264.
47. Mowat, C, Carswell, A, Wirz, A, et al. (1999) Omeprazole and dietary nitrate independently affect levels of vitamin C and nitrite in gastric juice. Gastroenterology 116, 813822.
48. Gago, B, Lundberg, JO, Barbosa, RM, et al. (2007) Red wine-dependent reduction of nitrite to nitric oxide in the stomach. Free Radic Biol Med 43, 12331242.
49. Lundberg, J & Weitzberg, E (2010) Chapter 16: Nitric oxide formation from inorganic nitrate and nitrite. In Nitric Oxide, 2nd ed., pp. 539–553 [LJ Ignarro, editor]. Burlington, MA: Academic Press.
50. Zhang, J, Villacorta, L, Chang, L, et al. (2010) Nitro-oleic acid inhibits angiotensin II–induced hypertension novelty and significance. Circ Res 107, 540548.
51. Satija, A, Stampfer, MJ, Rimm, EB, et al. (2018) Perspective: are large, simple trials the solution for nutrition research? Adv Nutr 9, 378387.
52. Bhupathiraju, SN, Wedick, NM, Pan, A, et al. (2013) Quantity and variety in fruit and vegetable intake and risk of coronary heart disease. Am J Clin Nutr 98, 15141523.
53. Colla, G, Kim, H-J, Kyriacou, MC, et al. (2018) Nitrate in fruits and vegetables. Sci Hortic 237, 221238.
54. European Food Safety Authority (EFSA) (2008) Nitrate in vegetables scientific opinion of the panel on contaminants in the food chain. EFSA J 689, 179.
55. Correll, J, Bluhm, B, Feng, C, et al. (2011) Spinach: better management of downy mildew and white rust through genomics. Eur J Plant Pathol 129, 193205.
56. Ahluwalia, A, Gladwin, M, Coleman, GD, et al. (2016) Dietary nitrate and the epidemiology of cardiovascular disease: report from a National Heart, Lung, and Blood Institute Workshop. J Am Heart Assoc 5, e003402.
57. Fewtrell, L (2004) Drinking-water nitrate, methemoglobinemia, and global burden of disease: a discussion. Environ Health Perspect 112, 13711374.
58. Moore, LV & Thompson, FE (2015) Adults meeting fruit and vegetable intake recommendations – United States, 2013. MMWR Morb Mortal Wkly Rep 64, 709713.
59. Wright, J & Wang, C-Y (2010) Trends in Intake of Energy and Macronutrients in Adults from 1999–2000 through 2007–2008. Atlanta, GA: Centers for Disease Control and Prevention (CDC), National Center for Health Statistics.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Jackson et al. supplementary material
Table S1 and Figure S1

 Word (41 KB)
41 KB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed