Impact of high drinking water nitrate levels on the endogenous formation of apparent N-nitroso compounds in combination with meat intake in healthy volunteers

Abstract

Background Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor. Methods Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells. Results Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant. Conclusions Drinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC. Trial registration Dutch Trialregister: 29707. Registered 19th of October 2018. Retrospectively registered.

FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women

“…Regarding the genotoxic damage in lymphocytes, we found a high percentage of binucleated cells with micronuclei, binucleated cells with nucleoplasmic bridges and binucleated cells with bubble protrusion, in medium and high exposure groups. These results agree with findings reported by Andreassi et al (2001 ) they observed a higher frequency of micronucleated lymphocytes and suggest possible chromosome alterations in humans exposed to chronic long-term nitrate therapy, and van Breda et al (2019 ) reported the formation of N-nitroso compounds in faecal water caused by the consumption of nitrates in drinking water, vegetables, and cured meat. Increasing the excretion of nitrate in urine and the concentration of N-nitroso compounds during the exposure time.…”

The benefits and risks of beetroot juice consumption: a systematic review

“…The ATNC levels in fecal water of the participants significantly increased during the high drinking water nitrate period. The results show that drinking water nitrate can have a significant contribution to the endogenous formation of NOCs (van Breda et al 2019).…”

“…It was concluded that nitrate intake at acceptable daily intake level combined with an amine rich meal leads to an increase in potential carcinogenic N-nitrosamine excretion in the urine (Vermeer et al 1998). In a recent study from van Breda et al (2019), the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs in healthy volunteers was examined. Healthy subjects consumed either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks.…”

Replacement of Nitrite in Meat Products by Natural Bioactive Compounds Results in Reduced Exposure to N‐Nitroso Compounds: The PHYTOME Project

“…Nitrate in drinking water may be more important in NOC formation than nitrate intake through dietary consumption. [34][35][36] Therefore, we quantified the effect of drinking water nitrate on the formation of NOC in healthy volunteers on a high meat diet. During the first 6 weeks, participants were asked to consume bottled drinking water, which contained low nitrate levels (< 2 mg L −1 ).…”

“…Before and after the dietary intervention, gene expression changes may reflect the molecular responses that are involved in cancer preventive action of the added phytochemicals or reduced exposure to NOC. As it is known that nitrate in drinking water may be converted by oral bacteria into nitrite and thus contribute to the formation of NOCs in the large intestine, particularly when high drinking water nitrate is combined with high intake of red and processed meat, [34][35][36] this study also aims to quantify the effect of drinking water nitrate on NOC formation in healthy subjects consuming meat products with and without replacement of nitrite.…”