Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

Abstract

Introduction Nitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality. Methods In 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes––calculated using comprehensive food composition and national drinking water quality monitoring databases––and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality over 27 years were examined using restricted cubic splines within Cox proportional hazards models adjusting for demographic, lifestyle, and dietary confounders. Analyses were stratified by factors hypothesised to influence the formation of carcinogenic N-nitroso compounds (namely, smoking and dietary intakes of vitamin C, vitamin E, folate, and polyphenols). Results Plant-sourced nitrate intake was inversely associated with all-cause mortality [HRQ5vsQ1: 0.83 (0.80, 0.87)] while higher risks of all-cause mortality were seen for higher intakes of naturally occurring animal-sourced nitrate [1.09 (1.04, 1.14)], additive permitted meat-sourced nitrate [1.19 (1.14, 1.25)], and tap water-sourced nitrate [1.19 (1.14, 1.25)]. Similar source-dependent associations were seen for nitrite and for CVD-related and cancer-related mortality except that naturally occurring animal-sourced nitrate and tap water-sourced nitrate were not associated with cancer-related mortality and additive permitted meat-sourced nitrate was not associated with CVD-related mortality. No clear patterns emerged in stratified analyses. Conclusion Nitrate/nitrite from plant sources are inversely associated while those from naturally occurring animal-sources, additive-permitted meat sources, and tap water-sources are positively associated with mortality.

Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity

“…Given the recent change in public perception of nitrate as being beneficial rather than detrimental, there is an urgent need to reproduce our findings in other laboratories and animal models and to investigate the mechanisms of enhanced cardiac fibrosis and hepatic malignancy. This is especially important since epidemiological evidence is emerging that the effects of enhanced nitrate intake on cardiovascular health may be sourcespecific (109).…”