Association between Dietary Nitrate, Nitrite Intake, and Site-Specific Cancer Risk: A Systematic Review and Meta-Analysis

Findings are drawn entirely from observational case-control and cohort studies, which cannot establish causation and are subject to dietary-recall error and residual confounding by other diet and lifestyle factors. Site-specific effect sizes were generally modest (odds ratios close to 1), several associations were only significant in meta-regression and not in direct highest-vs-lowest comparisons, and included studies did not consistently distinguish vegetable-derived nitrate from processed-meat-derived nitrite exposure.

The authors' own stated limitations note that very few studies were available for each cancer site - some sites had three or fewer included studies - so site-specific results should be treated with caution. The review could not adjust for potential confounders such as dietary vitamin C, vitamin E, or folate intake, which other research suggests can modify nitrate/nitrite-cancer associations. Nitrate and nitrite intake definitions and units varied widely across the included studies (for example, dietary nitrite ranged from 0-2.4 mg/day in the bladder cancer analysis versus 0-22 mg/day in the stomach cancer analysis), which the authors acknowledge could itself contribute to the variation in associations observed across cancer sites.