We are delighted with this support from the WCRF, which enables us to investigate sources of nitrate and nitrit from both drinking water and dietary intake and link it to the risk of cancers of the colorectum, bladder and gastric cancer. This is an important research question, where more research is urgently needed to understand the association between nitrate consumption and cancer risk.
– Prof Anne Tjønneland
Grant awarded: November 2020
Background
Nitrate and nitrite are compounds found naturally in foods and drinking water. Vegetables such as spinach and lettuce are rich sources of nitrate, but crucially they also contain protective antioxidants and vitamins. However, nitrate and nitrite also enter the body through drinking water contaminated by agricultural fertilizers and through processed meats, where they are added as preservatives. When consumed without accompanying antioxidant compounds, nitrate and nitrite can be converted in the body into N-nitrosamines, a group of cancer-causing compounds.
Aims and objectives
This project investigated whether nitrate and nitrite from different sources (vegetables, drinking water, processed meats, animal foods) have different associations with cancer risk. We also examined whether certain populations—including smokers and individuals with low intake of protective nutrients—might be more vulnerable to harmful effects.
How the study was carried out
We studied 54,610 Danish adults aged 50-64 years who provided detailed dietary and lifestyle information between 1993-1997. We estimated source-specific nitrate and nitrite intake from vegetables and plant foods, naturally-occurring amounts in animal foods, additives in processed meats, and drinking water. Dietary intakes were calculated using comprehensive food composition databases, while drinking water exposure was estimated by linking participants’ residential addresses to water supply monitoring data. Participants were followed for 27 years through Denmark’s national cancer registry. We examined bowel, stomach, and bladder cancer incidence, as well as all-cause and cancer-specific mortality. Statistical analyses compared cancer rates among individuals with different exposure levels while adjusting for age, sex, smoking, body weight, and overall diet quality.
Results
Five studies examined 2,245 bowel cancers, 260 stomach cancers, 1,058 bladder cancers, 16,883 all-cause deaths, and 7,093 cancer deaths. Dietary nitrate and nitrite showed no association with bowel cancer; however, drinking water nitrate concentrations ≥9.25 mg/L were associated with 52% higher colon cancer rates—notably below the 50 mg/L European regulatory limit. Associations were particularly strong among smokers (77% higher) and individuals with low folate or flavonoid intake (67-85% higher). For stomach cancer, vegetable-sourced nitrite was associated with 37% lower risk, whereas animal-sourced nitrite and processed meat additives showed harmful associations, with additives associated with more than three-fold higher risk for nitrate and nearly two- fold for nitrite. Elevated drinking water nitrate was also associated with higher stomach cancer rates. No associations were observed for bladder cancer. Vegetable-sourced nitrate and nitrite were associated with 17- 24% lower mortality risk, while processed meat additives, animal sources, and drinking water were associated with higher mortality.
Conclusion
This research demonstrates that the source of nitrate and nitrite is critical in determining health effects. Drinking water nitrate was associated with elevated cancer risk at concentrations well below current regulatory limits, particularly among smokers and individuals with low antioxidant intake. Processed meat additives showed particularly strong associations with stomach cancer. In contrast, vegetable-sourced nitrate and nitrite were protective. These findings support public health recommendations to increase vegetable consumption and limit processed meat intake, while highlighting the urgent need to reconsider drinking water safety standards to protect population health.
Impact
This grant has acheived substantial and direct policy impact at both national and international levels. Their work promted a the Danish Ministry of Environmnet and Gender Equality to convene an international expert group to evaluate nitrate in drinking water. Their findings were referenced in the report as key evidence leading to the recommendation for an 88% reduction in the parametric value for nitrate in drinking water from 50 mg/L to 6 mg/L. Upon completion, the expert committee’s findings and recommendations will be communicated to the European Food Standards Agency and the World Health Organisation.
Grant publications
- Dorit W. Erichsen, Nicola P. Bondonno, Pratik Pokharel, Susanne Rosthøj, Catherine P. Bondonno, Liezhou Zhong, Jörg Schullehner, Torben Sigsgaard, Peter Fjeldstad Hendriksen, Frederik Dalgaard, Ole Raaschou-Nielsen, Jonathan M. Hodgson, Christina C. Dahm, Anja Olsen, Anne Tjønneland, Cecilie Kyrø, Source-specific nitrate and nitrite intake and association with colorectal cancer in the Danish Diet, Cancer and Health Cohort, Environment International, Volume 202, 2025, 109658, ISSN 0160-4120.
- Bondonno NP, Pokharel P, Bondonno CP, Erichsen DW, Zhong L, Schullehner J, Frederiksen K, Kyrø C, Hendriksen PF, Hodgson JM, Dalgaard F, Blekkenhorst LC, Raaschou-Nielsen O, Sigsgaard T, Dahm CC, Tjønneland A, Olsen A. Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study. Eur J Epidemiol. 2024 Aug;39(8):925-942. doi: 10.1007/s10654-024-01133-5. Epub 2024 May 28. PMID: 38802612; PMCID: PMC11410901.
- Erichsen DW, Pokharel P, Kyrø C, Schullehner J, Zhong L, Bondonno CP, Dalgaard F, Fjeldstad Hendriksen P, Sigsgaard T, Hodgson JM, Olsen A, Tjønneland A, Bondonno NP. Source-specific nitrate and nitrite intakes and associations with sociodemographic factors in the Danish Diet Cancer and Health cohort. Front Nutr. 2024 Feb 27;11:1326991. doi: 10.3389/fnut.2024.1326991. PMID: 38476601; PMCID: PMC10927827.
