Year: 2026 | Month: October | Volume: 13 | Issue: 10 | Pages: 322-341
DOI: https://doi.org/10.52403/ijrr.20261029
Endogenous Formation of Carcinogenic N-Nitrosamines from Dietary Nitrite: Mechanisms, Modulators, and Cancer Risk
Rushikesh Joshi1, Saloni Kulkarni2, Mugdha Pradhan3
1M.Pharm., Researcher, ThriveTribe Wellness Solutions Private Limited, Pune, India
2M.Sc., Head of Client Services, ThriveTribe Wellness Solutions Private Limited, Pune, India
3M.Sc., Expert Functional Nutritionist and CEO, ThriveTribe Wellness Solutions Private Limited, Pune, India
Corresponding Author: Rushikesh Joshi
ABSTRACT
Nitrite dietary intake is utilized widely in the curing and processing of meats for their antimicrobial action, Clostridium botulinum inhibition, as well as for their role in imparting meat color and flavor. Yet, nitrite can become involved in endogenous N-nitrosation, resulting in the formation of N-nitrosamines and other N-nitrosocompounds (NOCs), including N-nitrosodimethylamine (NDMA), following consumption. The present review focuses on the chemistry, gastrointestine physiology, microbial action, toxicity, epidemiology, and regulation of this phenomenon. Nitrite, in an acidic environment of the stomach, is transformed into nitrous acid and nitrosating intermediates, such as nitrosonium derivatives and dinitrogen trioxide, which react with secondary amines and amides. In cases of hypochlorhydric or achlorhydria, bacterial involvement can provide an alternative mechanism. Additionally, the review also draws a distinction between food sources where, as observed, nitrate-containing vegetables make an important contribution to the body’s nitrate-nitrite burden, although their high level of vitamin C and polyphenols would inhibit nitrosation. Some other sources include heme iron, thiocyanates, carbonyl compounds, dietary amines, and selected microbial processes that facilitate the production of NOCs while ascorbate, tocopherol, polyphenols, and thiols prevent this reaction from taking place. Once metabolically activated, NDMA may be involved in the creation of DNA reactive electrophiles such as methyl diazonium that lead to mutagenic DNA adducts such as O6-methylguanine. The epidemiological observations differ depending on the type of cancer and source of exposure, with more consistent results being obtained for gastric cancer as compared to colorectal, oesophageal or pancreatic cancer. The review also mentions limitations of concentration-based assessments and suggests several methods such as source-resolved exposure assessment, biomarkers, physiologically based pharmacokinetic models and nitrosation potential index. Special emphasis is placed on the difference between chemical plausibility, biomarker data, epidemiological observations and causal inference.
Keywords: Dietary Nitrosamine, Endogenous nitrosamine, Nitrate, Nitrile.
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