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Drinking Water Nitrate and Human Health: An Updated Review

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Ward, Mary, Jones, Rena, Brender, Jean, De Kok, Theo, Weyer, Peter, Nolan, Bernard, Villanueva, Cristina, Van Breda, Simone·2018·International Journal of Environmental Research and Public Health
DOI 10.3390/ijerph15071557PMC PMC6068531
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Abstract

Nitrate levels in our water resources have increased in many areas of the world largely due to applications of inorganic fertilizer and animal manure in agricultural areas. The regulatory limit for nitrate in public drinking water supplies was set to protect against infant methemoglobinemia, but other health effects were not considered. Risk of specific cancers and birth defects may be increased when nitrate is ingested under conditions that increase formation of N-nitroso compounds. We previously reviewed epidemiologic studies before 2005 of nitrate intake from drinking water and cancer, adverse reproductive outcomes and other health effects. Since that review, more than 30 epidemiologic studies have evaluated drinking water nitrate and these outcomes. The most common endpoints studied were colorectal cancer, bladder, and breast cancer (three studies each), and thyroid disease (four studies). Considering all studies, the strongest evidence for a relationship between drinking water nitrate ingestion and adverse health outcomes (besides methemoglobinemia) is for colorectal cancer, thyroid disease, and neural tube defects. Many studies observed increased risk with ingestion of water nitrate levels that were below regulatory limits. Future studies of these and other health outcomes should include improved exposure assessment and accurate characterization of individual factors that affect endogenous nitrosation.

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  • These mechanisms are particularly relevant in older adults with reduced endogenous antioxidant capacity and impaired NO signalling.

    “mechanisms that are particularly relevant in older adults with reduced endogenous antioxidant capacity and impaired NO signalling [185,288].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [288]

    Section 4 (page unavailable) discusses nitric oxide’s physiological effects and the inhibition of nitrosation by dietary antioxidants. Section 9 (page unavailable) discusses possible nitrate-related cardiovascular benefits, but the review does not say these mechanisms are particularly relevant in older adults or that older adults have reduced endogenous antioxidant capacity and impaired NO signalling. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Fresh and minimally processed vegetables retain native nitrate content and vitamin C, betalains and flavonoids, which stabilise nitrite, limit oxidative degradation of NO and support S-nitrosothiol formation.

    “Fresh and minimally processed vegetables retain not only their native nitrate content but also vitamin C, betalains and flavonoids, which stabilise nitrite, limit oxidative degradation of NO and support S-nitrosothiol formation”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [288]

    Section 4 (page unavailable) describes nitrate-rich vegetables that also contain natural nitrosation inhibitors, and says vitamin C and some polyphenols can promote conversion of nitrous acid or nitrite to NO. It does not establish that fresh or minimally processed vegetables retain the listed compounds, mention betalains, or support the claimed effects on nitrite stability, oxidative degradation of NO, or S-nitrosothiol formation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Highly processed nitrate-containing foods often undergo thermal treatment or prolonged storage, which diminishes phytochemical content and may reduce nitrate stability.

    “highly processed nitrate-containing foods often undergo thermal treatment or prolonged storage, which diminishes phytochemical content and may reduce nitrate stability [210,215,288].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [288]

    Section 4 discusses dietary antioxidants, nitrate-rich vegetables, and processed meat, but does not say that thermal treatment or prolonged storage diminishes phytochemicals or reduces nitrate stability. Searches for storage, heating, and processing found no passage addressing those effects. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Ward, M., Jones, R., Brender, J., De Kok, T., Weyer, P., Nolan, B., Villanueva, C., & Van Breda, S.
Affiliations
  • National Cancer Institute (US)
  • Texas A&M University (US)
  • Department of Toxicogenomics, GROW-school for Oncology and Developmental Biology, Maastricht University Medical Center, P.O Box 616, 6200 MD Maastricht, The Netherlands
  • University of Iowa (US)
  • United States Geological Survey (US)
  • Universitat Pompeu Fabra (ES)
Corresponding author
Ward, Mary
ORCID
Venue
International Journal of Environmental Research and Public Health
Publisher
MDPI AG
Published
2018-07-23
Volume
15
Issue
7
Pages
1557
ISSN
1660-4601 (ISSN-L)
DOI
10.3390/ijerph15071557
PMC
PMC6068531
OpenAlex
W2884859931
Cited by
1,576
References
13
Citations by year
2026: 244 · 2025: 270 · 2024: 246 · 2023: 206 · 2022: 230 · 2021: 194 · 2020: 133 · 2019: 50 · 2018: 2
FWCI
9.95
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Environmental Research and Public Health (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion, cc-by)
Funders
  • Intramural Research Program of the U.S. National Cancer Institute (Z01 CP010125-23)
  • European Commission 7th Framework programme for Research and Technology, PHYTOME project (EU-FP7 grant agreement no. 315683)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Water Treatment and Disinfection
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
Keywords
drinking water nitrate, nitrate ingestion, colorectal cancer, bladder cancer, breast cancer, thyroid dysfunction, neural tube defects, congenital malformations, N-nitroso compounds, endogenous nitrosation, fertilizer runoff, livestock manure, exposure assessment
MeSH terms
Animals, Environmental Monitoring, Europe, Female, Humans, Methemoglobinemia, Neoplasms, Neural Tube Defects, Nitrates, Nitroso Compounds, Pregnancy, Thyroid Diseases, United States, Water Pollutants, Chemical, Drinking Water

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