Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

doi:10.1007/s10654-024-01133-5

. 2024 May 28.

doi: 10.1007/s10654-024-01133-5. Online ahead of print.

Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

Nicola P Bondonno^{1

2}, Pratik Pokharel^{3

4}, Catherine P Bondonno^{4

5}, Dorit W Erichsen³, Liezhou Zhong^{4

6}, Jörg Schullehner^{7

8}, Kirsten Frederiksen³, Cecilie Kyrø³, Peter Fjeldstad Hendriksen³, Jonathan M Hodgson^{4

5}, Frederik Dalgaard⁹, Lauren C Blekkenhorst^{4

5}, Ole Raaschou-Nielsen^{3

10}, Torben Sigsgaard^{8

11}, Christina C Dahm⁸, Anne Tjønneland^{3

12}, Anja Olsen^{3

8}

Affiliations

¹ The Danish Cancer Institute, Copenhagen, Denmark. n.bondonno@ecu.edu.au.
² Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia. n.bondonno@ecu.edu.au.
³ The Danish Cancer Institute, Copenhagen, Denmark.
⁴ Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
⁵ Medical School, The University of Western Australia, Royal Perth Hospital, Perth, WA, Australia.
⁶ Institute of Agriculture, The University of Western Australia, Royal Perth Hospital, Perth, WA, Australia.
⁷ Department of Groundwater and Quaternary Geology Mapping, Geological Survey of Denmark and Greenland, Aarhus, Denmark.
⁸ Department of Public Health, Aarhus University, Aarhus, Denmark.
⁹ Department of Cardiology, Herlev & Gentofte University Hospital, Copenhagen, Denmark.
¹⁰ Department of Environmental Science, Aarhus University, Roskilde, Denmark.
¹¹ Danish Big Data Centre for Environment and Health (BERTHA), Aarhus University, Aarhus, Denmark.
¹² Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

PMID: 38802612
DOI: 10.1007/s10654-024-01133-5

Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

Nicola P Bondonno et al. Eur J Epidemiol. 2024.

. 2024 May 28.

doi: 10.1007/s10654-024-01133-5. Online ahead of print.

Authors

Affiliations

¹ The Danish Cancer Institute, Copenhagen, Denmark. n.bondonno@ecu.edu.au.
² Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia. n.bondonno@ecu.edu.au.
³ The Danish Cancer Institute, Copenhagen, Denmark.
⁴ Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
⁵ Medical School, The University of Western Australia, Royal Perth Hospital, Perth, WA, Australia.
⁶ Institute of Agriculture, The University of Western Australia, Royal Perth Hospital, Perth, WA, Australia.
⁷ Department of Groundwater and Quaternary Geology Mapping, Geological Survey of Denmark and Greenland, Aarhus, Denmark.
⁸ Department of Public Health, Aarhus University, Aarhus, Denmark.
⁹ Department of Cardiology, Herlev & Gentofte University Hospital, Copenhagen, Denmark.
¹⁰ Department of Environmental Science, Aarhus University, Roskilde, Denmark.
¹¹ Danish Big Data Centre for Environment and Health (BERTHA), Aarhus University, Aarhus, Denmark.
¹² Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

PMID: 38802612
DOI: 10.1007/s10654-024-01133-5

Abstract

Introduction: Nitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality.

Methods: In 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes--calculated using comprehensive food composition and national drinking water quality monitoring databases--and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality over 27 years were examined using restricted cubic splines within Cox proportional hazards models adjusting for demographic, lifestyle, and dietary confounders. Analyses were stratified by factors hypothesised to influence the formation of carcinogenic N-nitroso compounds (namely, smoking and dietary intakes of vitamin C, vitamin E, folate, and polyphenols).

Results: Plant-sourced nitrate intake was inversely associated with all-cause mortality [HR_Q5vsQ1: 0.83 (0.80, 0.87)] while higher risks of all-cause mortality were seen for higher intakes of naturally occurring animal-sourced nitrate [1.09 (1.04, 1.14)], additive permitted meat-sourced nitrate [1.19 (1.14, 1.25)], and tap water-sourced nitrate [1.19 (1.14, 1.25)]. Similar source-dependent associations were seen for nitrite and for CVD-related and cancer-related mortality except that naturally occurring animal-sourced nitrate and tap water-sourced nitrate were not associated with cancer-related mortality and additive permitted meat-sourced nitrate was not associated with CVD-related mortality. No clear patterns emerged in stratified analyses.

Conclusion: Nitrate/nitrite from plant sources are inversely associated while those from naturally occurring animal-sources, additive-permitted meat sources, and tap water-sources are positively associated with mortality.

Keywords: Meat; Mortality; Nitrate; Nitrite; Vegetables; Water.

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References

1. Bondonno CP, Zhong L, Bondonno NP, et al. Nitrate: the Dr. Jekyll and Mr. Hyde of human health? Trends in Food Science & Technology; 2023.
1. Viets FG, Hageman RH. Factors affecting the accumulation of nitrate in soil, water, and plants. Agricultural Research Service, US Department of Agriculture; 1971.
1. Van Faassen EE, Bahrami S, Feelisch M, et al. Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev. 2009;29(5):683–741. - PubMed - PMC - DOI
1. Flores M, Toldrá F. Chemistry, safety, and regulatory considerations in the use of nitrite and nitrate from natural origin in meat products-invited review. Meat Sci. 2021;171:108272. - PubMed - DOI
1. Bian Z, Wang Y, Zhang X, et al. A review of environment effects on nitrate accumulation in leafy vegetables grown in controlled environments. Foods. 2020;9(6):732. - PubMed - PMC - DOI

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[1] Bondonno CP, Zhong L, Bondonno NP, et al. Nitrate: the Dr. Jekyll and Mr. Hyde of human health? Trends in Food Science & Technology; 2023.

[2] Bondonno CP, Zhong L, Bondonno NP, et al. Nitrate: the Dr. Jekyll and Mr. Hyde of human health? Trends in Food Science & Technology; 2023.

[3] Viets FG, Hageman RH. Factors affecting the accumulation of nitrate in soil, water, and plants. Agricultural Research Service, US Department of Agriculture; 1971.

[4] Viets FG, Hageman RH. Factors affecting the accumulation of nitrate in soil, water, and plants. Agricultural Research Service, US Department of Agriculture; 1971.

[5] Van Faassen EE, Bahrami S, Feelisch M, et al. Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev. 2009;29(5):683–741. - PubMed - PMC - DOI

[6] Van Faassen EE, Bahrami S, Feelisch M, et al. Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev. 2009;29(5):683–741. - PubMed - PMC - DOI

[7] Flores M, Toldrá F. Chemistry, safety, and regulatory considerations in the use of nitrite and nitrate from natural origin in meat products-invited review. Meat Sci. 2021;171:108272. - PubMed - DOI

[8] Flores M, Toldrá F. Chemistry, safety, and regulatory considerations in the use of nitrite and nitrate from natural origin in meat products-invited review. Meat Sci. 2021;171:108272. - PubMed - DOI

[9] Bian Z, Wang Y, Zhang X, et al. A review of environment effects on nitrate accumulation in leafy vegetables grown in controlled environments. Foods. 2020;9(6):732. - PubMed - PMC - DOI

[10] Bian Z, Wang Y, Zhang X, et al. A review of environment effects on nitrate accumulation in leafy vegetables grown in controlled environments. Foods. 2020;9(6):732. - PubMed - PMC - DOI

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Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

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Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

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