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

Abstract

Background: People consume nitrates, nitrites, nitrosamines, and NOCs compounds primarily through processed food. Many studies have yielded inconclusive results regarding the association between cancer and dietary intakes of nitrates and nitrites. This study aimed to quantify these associations across the reported literature thus far. Methods: We performed a systematic review following PRISMA and MOOSE guidelines. A literature search was performed using Web of Science, Embase, PubMed, the Cochrane library, and google scholar up to January 2020. STATA version 12.0 was used to conduct meta-regression and a two-stage meta-analysis. Results: A total of 41 articles with 13 different cancer sites were used for analysis. Of these 13 cancer types/sites, meta-regression analysis showed that bladder and stomach cancer risk was greater, and that pancreatic cancer risk was lower with increasing nitrite intakes. Kidney and bladder cancer risk were both lower with increasing nitrate intakes. When comparing highest to lowest (reference) categories of intake, meta-analysis of studies showed that high nitrate intake was associated with an increased risk of thyroid cancer (OR = 1.40, 95% CI: 1.02, 1.77). When pooling all intake categories and comparing against the lowest (reference) category, higher nitrite intake was associated with an increased risk of glioma (OR = 1.12, 95% CI: 1.03, 1.22). No other associations between cancer risk and dietary intakes of nitrates or nitrites were observed. Conclusion: This study showed varied associations between site-specific cancer risks and dietary intakes of nitrate and nitrite. Glioma, bladder, and stomach cancer risks were higher and pancreatic cancer risk was lower with higher nitrite intakes, and thyroid cancer risk was higher and kidney cancer risk lower with higher nitrate intakes. These data suggest type- and site-specific effects of cancer risk, including protective effects, from dietary intakes of nitrate and nitrite.

Caloric Restriction (CR) Plus High-Nitrate Beetroot Juice Does Not Amplify CR-Induced Metabolic Adaptation and Improves Vascular and Cognitive Functions in Overweight Adults: A 14-Day Pilot Randomised Trial

“…Epidemiological studies have suggested a potential carcinogenic association with dietary nitrate [ 80 , 81 ]. However, the evidence of the association of dietary nitrate intake with cancer risk is still mixed [ 82 ], which may be confounding by the consumption of processed meats containing nitrates and nitrites used as food preservatives [ 82 ]. The current WHO acceptable and recommended daily intake for nitrate is 3.7 mg/kg/day or lower, which approximately ranges from 260 mg/day to 370 mg/day of nitrate in individuals with a body weight between 70 and 100 kg.…”

N‐Nitrosamines: a potential hazard in processed meat products

“…An increased risk of thyroid cancer has been linked to high nitrate intake. 29 Furthermore, there is a positive correlation between eating processed beef and the risk of developing type 2 diabetes and cardiovascular disease. 30 According to the majority of casecontrol studies, intake of processed meat raises the risk of developing esophageal and gastric cancer, while intake of meat, processed meat, and smoked meals raises the risk of developing gastric cancer.…”

“…75 In another metaanalysis study, it is stated that intake of nitrate and nitrite, which are nitrosamine precursors, is positively associated with colon, rectum, esophageal, pancreatic, kidney, thyroid, and glioma cancers. 29 An important risk factor for the development of stomach cancer is nutrition and nutrients. Nutrition and cancer incidence have been linked, according to a chromatographic analysis of the Nnitrosamine concentration in gastric juice.…”

“…81 In a metaanalysis of the effects of nitrosamines on specific cancer types, high nitrate intake is associated with thyroid cancer, while NDMA intake is positively associated with the risk of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in men. 29 On the other hand, consumption of red and processed meat has been associated with an increase in developing lung cancer, with 12.2 ng 100 g −1 being the highest possible risk level. 82 A daily consumption of 54.5 ng dietary nitrosamines is associated with the highest risk of bladder cancer in a study of never-smokers.…”

Highly Sensitive Graphene-Based Electrochemical Sensor for Nitrite Assay in Waters

“…3 ), as a result of microorganisms in our saliva, stomach and intestines [9]. It has long been acknowledged that serious, harmful health consequences (such as respiratory distress, central nervous system problems, carcinogenic tumors, thyroid affections, genetic modifications, and even death) might occur from nitrite overexposure [10][11][12][13] High nitrite levels lead to a serious blood condition called methemoglobinemia or 'Blue Baby Syndrome', in which the body is deprived of oxygen, since nitrites oxidize the iron component of red blood cells (hemoglobin), causing them to lose their ability to transport oxygen [14]. In view of all of these health posing risks, the World Health Organization (WHO) has established guidelines on acceptable levels of human intake based on the lack of particular short-term health consequences (methemoglobinemia and thyroid effects).…”