How do nitrates and nitrites in cured meats chemically form N‑nitroso compounds in the human body?

1. The molecular players: nitrate, nitrite and nitrosatable amines

Nitrate itself is relatively inert toward direct nitrosation; it becomes relevant after biotransformation to nitrite, which under acidic conditions generates nitrous acid and derived nitrosating species that attack amines and amides to form N‑nitroso compounds ^{[5] [2]}. The amine substrates include secondary amines and some amides and degradation products of dietary protein; primary amines tend to be deaminated or give unstable products, while tertiary amines are less reactive in nitrosation reactions ^{[1] [4]}.

2. Stepwise chemistry: how NOCs form in the gut

The basic chemical sequence documented across reviews is nitrate → nitrite (microbial or enzymatic reduction) → protonation to nitrous acid (HNO2) at low pH → nitrosation of amines to give N‑nitroso compounds; mechanistically, nitrous acid or derived nitrosating electrophiles transfer a nitroso (–N=O) group to an amine, yielding an N‑nitrosamine or related NOC ^{[1] [6] [5]}. This nitrosation pathway is the canonical chemical route cited by ATSDR, WHO/IARC summaries and mechanistic reviews ^{[2] [7] [6]}.

3. Where in the body this chemistry actually occurs

The stomach—because of its low pH and relatively high exposure to swallowed nitrite—is regarded as the principal site for chemical nitrosation, especially of secondary amines, producing stable N‑nitrosamines ^{[2] [8]}. Oral bacteria under the tongue convert much dietary nitrate to nitrite before swallowing, concentrating nitrite in saliva and seeding the stomach’s substrate pool ^{[1] [3]}. Chemical nitrosation is less favored in the near‑neutral colon milieu, though microbial nitrosation and local production of amines can support some NOC formation there under specific bacterial and pH microenvironments ^{[1] [5]}.

4. Biological and dietary modifiers that amplify or suppress nitrosation

Several factors alter the balance between benign nitrogen chemistry and harmful nitrosation: low gastric pH and available nitrite increase nitrosation rates, heme iron from red meat promotes NOC formation, and certain gut microbes can mediate nitrosation in the intestine ^{[4] [5] [1]}. Conversely, antioxidants such as vitamin C and other inhibitors found in vegetables block nitrosation by reducing nitrosating species or intercepting intermediates; this partly explains why nitrate‑rich vegetables are not epidemiologically linked to the same risk as processed meats ^{[4] [3] [9]}.

5. Which N‑nitroso compounds matter for health—and what the evidence says

Many NOCs are carcinogenic in animal models and some are strongly suspected or classified as probable human carcinogens; IARC concluded that conditions leading to endogenous nitrosation render ingested nitrate/nitrite probably carcinogenic under those conditions (Group 2A) ^{[2] [9]}. Epidemiological and experimental literature is complex and heterogeneous: formation of specific nitrosamines (e.g., nitrosodimethylamine) depends on substrate availability in food and gut, and industry practices (curing) can also introduce preformed NOCs ^{[6] [10] [4]}.

6. Bottom line and limits of certainty

Mechanistically, the pathway from nitrate to nitrite to nitrous acid to nitrosation of amines is well established and biochemically plausible as a source of N‑nitroso compounds in humans; the real‑world risk depends on exposure context—nitrite dose, amine substrates, stomach acidity, microbial activity, presence of promotors like heme iron and inhibitors like vitamin C—and epidemiological attribution remains nuanced ^{[1] [2] [4]}. The provided sources document chemical mechanisms and modulators but do not resolve the precise quantitative cancer risk for any individual; where sources differ, they converge on the same mechanistic chain while emphasizing that dietary matrix and host factors control outcomes ^{[5] [3]}.