Nitrate: The Dr. Jekyll and Mr. Hyde of human health?

Background: Dietary nitrate has a controversial role in human health. For over half a century, the nitrate content of the three major dietary sources – vegetables, meat, and water – has been legislated, regulated, and monitored due to public health concerns over cancer risk. In contrast, a growing and compelling body of evidence indicates that dietary nitrate, particularly from vegetables, protects against cardiovascular disease and other chronic diseases. This evidence for the protective effect of nitrate is overshadowed by the potential for nitrate to form carcinogenic N-nitrosamines. Scope and approach: The nitrate content, regulations and estimated intake from vegetables, meat and water are described. The evidence that nitrate, through its effects on nitric oxide, improves cardiovascular disease outcomes, cognitive health, musculoskeletal health, and exercise performance as well as the potential to protect against other debilitating health outcomes (nitrate as Dr Jekyll) is discussed. The underlying assumption that all nitrate, irrespective of source, leads to the formation of carcinogenic N-nitrosamines and the evidence of an association between the different sources of nitrate and cancer (nitrate as Mr Hyde) is examined. Key findings and conclusions: The current theory that nitrate, is a carcinogenic contaminant in meat, water, and vegetables is not fully supported by available evidence. Definitive studies examining the beneficial or harmful effects of source-dependent nitrate have yet to be performed. Studies with improved exposure assessment and accurate characterization of factors that affect endogenous nitrosation are also needed to draw conclusions about risk of cancer from dietary nitrate intake

Data_Sheet_1_Source-specific nitrate and nitrite intakes and associations with sociodemographic factors in the Danish Diet Cancer and Health cohort.docx

BackgroundThe dietary source and intake levels of nitrate and nitrite may govern its deleterious versus beneficial effects on human health. Existing evidence on detailed source-specific intake is limited. The objectives of this study were to assess nitrate and nitrite intakes from different dietary sources (plant-based foods, animal-based foods, and water), characterize the background diets of participants with low and high intakes, and investigate how sociodemographic and lifestyle factors associate with intake levels.MethodsIn the Danish Diet, Cancer and Health Cohort, sociodemographic and lifestyle information was obtained from participants at enrolment (1993–1997). Source-dependent nitrate and nitrite intakes were calculated using comprehensive food composition databases, with tap water nitrate intakes estimated via the national drinking water quality monitoring database linked with participants’ residential addresses from 1978 to 2016. Underlying dietary patterns were examined using radar plots comparing high to low consumers while sociodemographic predictors of source-dependent nitrate intakes were investigated using linear regression models.ResultsIn a Danish cohort of 55,754 participants aged 50–65 at enrolment, the median [IQR] intakes of dietary nitrate and nitrite were 58.13 [44.27–74.90] mg/d and 1.79 [1.43–2.21] mg/d, respectively. Plant-based foods accounted for ~76% of nitrate intake, animal-based foods ~10%, and water ~5%. Nitrite intake was sourced roughly equally from plants and animals. Higher plant-sourced nitrate intake was associated with healthier lifestyles, better dietary patterns, more physical activity, higher education, lower age and lower BMI. Females and participants who had never smoked also had significantly higher plant-sourced nitrate intakes. Higher water-sourced nitrate intake was linked to sociodemographic risk factors (smoking, obesity, lower education). Patterns for animal-sourced nitrate were less clear.ConclusionParticipants with higher plant-sourced nitrate intakes tend to be healthier while participants with higher water-sourced nitrate intakes tended to be unhealthier than their low consuming counterparts. Future research in this cohort should account for the sociodemographic and dietary predictors of source-specific nitrate intake we have identified.</p

The contact system—a novel branch of innate immunity generating antibacterial peptides

Activation of the contact system has two classical consequences: initiation of the intrinsic pathway of coagulation, and cleavage of high molecular weight kininogen (HK) leading to the release of bradykinin, a potent proinflammatory peptide. In human plasma, activation of the contact system at the surface of significant bacterial pathogens was found to result in further HK processing and bacterial killing. A fragment comprising the D3 domain of HK is generated, and within this fragment a sequence of 26 amino acids is mainly responsible for the antibacterial activity. A synthetic peptide covering this sequence kills several bacterial species, also at physiological salt concentration, as effectively as the classical human antibacterial peptide LL-37. Moreover, in an animal model of infection, inhibition of the contact system promotes bacterial dissemination and growth. These data identify a novel and important role for the contact system in the defence against invasive bacterial infection