Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (Delta(max) -10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a "natural" low cost approach for the treatment of cardiovascular disease.

/pdf/acute-blood-pressure-lowering-vasoprotective-and-unx6ngo3h7.pdf

Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite

Nitrate content is an important quality characteristic of vegetables. Vegetable nitrate content is of interest to governments and regulators owing to the possible implications for health and to check that controls on the content are effective. Nitrate itself is relatively non-toxic but its metabolites may produce a number of health effects. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Recent research studies suggest that nitrate is actually a key part of our bodies' defences against gastroenteritis. In this review are reported: (1) vegetable classification as a function of nitrate accumulation; (2) vegetable contribution to the total dietary exposure of nitrate; (3) European Commission Regulation No. 563/2002 which sets limits for nitrate in lettuce and spinach; (4) the maximum levels set in some countries for beetroot, cabbage, carrot, celery, endive, Lamb's lettuce, potato, radish and rocket; (5) the results of surveys on the nitrate content of vegetables in Italy and other European countries.  2005 Society of Chemical Industry

/pdf/nitrate-in-vegetables-toxicity-content-intake-and-ec-16krz1y7v4.pdf

Nitrate in vegetables: toxicity, content, intake and EC regulation

https://www.meatinstitute.org/index.php?ht=a/GetDocumentAction/i/50895

Food sources of nitrates and nitrites: the physiologic context for potential health benefits

Introduction Nitric Oxide Source of NO in exhaled air Measurement Asthma COPD Cystic fibrosis Bronchiectasis Primary ciliary dyskinesia Rhinitis Interstitial lung diseases Pulmonary hypertension Occupational diseases Infections Chronic cough Lung cancer Lung transplant rejection Adult respiratory distress syndrome Diffuse Panbronchiolitis Carbon Monoxide Source of exhaled CO Measurement Asthma COPD Bronchiectasis Cystic fibrosis Interstitial lung disease Allergic rhinitis Infections Other conditions Exhaled Hydrocarbons Origin Measurement Asthma COPD Cystic Fibrosis Other lung diseases Exhaled Breath Condensate Origin Hydrogen peroxide Eicosanoids Products of lipid peroxidation Vasoactive amines NO-related products Ammonia Electrolytes Hydrogen ions Proteins and cytokines Other Methods Exhaled temperature Combined gas chromatography/spectroscopy The selected ion flow tube (SIFT) technique Polymer-coated surface-acoustic-wave resonators Future Directions Standardization of measurements Clinical application Profiles of mediators Measuring devices New markers

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.163.7.2009041

Exhaled markers of pulmonary disease.

Nitrate is generally considered a water pollutant and an undesirable fertilizer residue in the food chain Research in the 1970s indicated that, by reducing nitrate to nitrite, commensal bacteria might be involved in the pathogenesis of gastric cancers and other malignancies, as nitrite can enhance the generation of carcinogenic N-nitrosamines More recent studies indicate that the bacterial metabolism of nitrate to nitrite and the subsequent formation of biologically active nitrogen oxides could be beneficial Here, we will consider the evidence that nitrate-reducing commensals have a true symbiotic role in mammals and facilitate a previously unrecognized but potentially important aspect of the nitrogen cycle

Nitrate, bacteria and human health.

BACKGROUND/AIMS: It has been suggested that dietary nitrate, after concentration in the saliva and reduction to nitrite by tongue surface bacteria, is chemically reduced to nitric oxide (NO) in the acidic conditions of the stomach. This study aimed to quantify this in humans. METHODS: Ten healthy fasting volunteers were studied twice, after oral administration of 2 mmol of potassium nitrate or potassium chloride. Plasma, salivary and gastric nitrate, salivary and gastric nitrite, and gastric headspace NO concentrations were measured over six hours. RESULTS: On the control day the parameters measured varied little from basal values. Gastric nitrate concentration was 105.3 (13) mumol/l (mean (SEM), plasma nitrate concentration was 17.9 (2.4) mumol/l, salivary nitrate concentration 92.6 (31.6) mumol/l, and nitrite concentration 53.9 (22.8) mumol/l. Gastric nitrite concentrations were minimal (< 1 mumol/l). Gastric headspace gas NO concentration was 16.4 (5.8) parts per million (ppm). After nitrate ingestion, gastric nitrate peaked at 20 minutes at 3430 (832) mumol/l, plasma nitrate at 134 (7.2) mumol/l, salivary nitrate at 1516.7 (280.5) mumol/l, and salivary nitrite at 761.5 (187.7) mumol/l after 20-40 minutes. Gastric nitrite concentrations tended to be low, variable, and any rise was non-sustained. Gastric NO concentrations rose considerably from 14.8 (3.1) ppm to 89.4 (28.6) ppm (p < 0.0001) after 60 minutes. All parameters remained increased significantly for the duration of the study. CONCLUSIONS: A very large and sustained increase in chemically derived gastric NO concentrations after an oral nitrate load was shown, which may be important both in host defence against swallowed pathogens and in gastric physiology.

https://gut.bmj.com/content/gutjnl/40/2/211.full.pdf

Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans.

Based on the premise that dietary nitrate is detrimental to human health, increasingly stringent regulations are being instituted to lower nitrate levels in food and water. Not only does this pose a financial challenge to water boards and a threat to vegetable production in Northern Europe, but also may be eliminating an important non-immune mechanism for host defence. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Epidemiological studies have failed to substantiate this. It has been shown that dietary nitrate undergoes enterosalivary circulation. It is recirculated in the blood, concentrated by the salivary glands, secreted in the saliva and reduced to nitrite by facultative Gram-positive anaerobes (Staphylococcus sciuri and S. intermedius) on the tongue. Salivary nitrite is swallowed into the acidic stomach where it is reduced to large quantities of NO and other oxides of N and, conceivably, also contributes to the formation of systemic S-nitrosothiols. NO and solutions of acidified nitrite, mimicking gastric conditions, have been shown to have antimicrobial activity against a wide range of organisms. In particular, acidified nitrite is bactericidal for a variety of gastrointestinal pathogens such as Yersinia and Salmonella. NO is known to have vasodilator properties and to modulate platelet function, as are S-nitrosothiols. Thus, nitrate in the diet, which determines reactive nitrogen oxide species production in the stomach (McKnight et al. 1997), is emerging as an effective host defence against gastrointestinal pathogens, as a modulator of platelet activity and possibly even of gastrointestinal motility and microcirculation. Therefore dietary nitrate may have an important therapeutic role to play, not least in the immunocompromised and in refugees who are at particular risk of contracting gastroenteritides.

/pdf/dietary-nitrate-in-man-friend-or-foe-3pfrc574ez.pdf

Dietary nitrate in man: friend or foe?

BACKGROUND: In subjects on a low nitrate diet, plasma nitrate concentration and urinary nitrate excretion are thought to reflect endogenous nitric oxide (NO) production, and have been reported to increase during infective and inflammatory bowel disease. AIMS: To compare the extent of NO production in patients with infective versus non-infective forms of bowel dysfunction. SUBJECTS: Four groups: 20 healthy, volunteer clerical and laboratory staff, 12 patients with irritable bowel syndrome, 19 patients with inflammatory bowel disease, and 20 patients with infective gastroenteritis. METHODS: The plasma nitrate concentration was determined with a copper coated cadmium column and spectrophotometry. Mean and median plasma nitrate concentrations were calculated and compared within the four groups. Mann-Whitney distribution free rank testing was used to compare the median values. RESULTS: Median plasma nitrate concentrations in the four groups were: controls 32.7 mumol/l; irritable bowel syndrome 35.5 mumol/l; inflammatory bowel disease 35.1 mumol/l; and gastroenteritis 117.9 mumol/l (p < 0.001 gastroenteritis v all other groups). CONCLUSIONS: Plasma nitrate concentration could serve as a discriminant between infective and inflammatory or functional bowel disease in patients presenting with diarrhoea. It is not clear why there is considerable difference in endogenous nitrate synthesis in these two conditions, which are both characterised by severe gut inflammation.

https://gut.bmj.com/content/gutjnl/39/3/393.full.pdf

Plasma nitrate concentration in infective gastroenteritis and inflammatory bowel disease

Background/Aims-It hasbeensuggested thatdietary nitrate, after concentration in thesalivaand reduction to nitrite by tonguesurfacebacteria, ischemically reduced tonitric oxide(NO)intheacidic conditions ofthestomach.Thisstudy aimedtoquantify thisinhumans. Methods-Tenhealthy fasting volunteers werestudied twice, afteroraladministration of2mmolofpotassium nitrate or potassium chloride. Plasma, salivary and gastric nitrate, salivary andgastric nitrite, andgastric headspace NO concentrations weremeasured oversixhours. Results-Onthecontroldaytheparametersmeasured varied little frombasal values. Gastric nitrate concentration was 105-3(13)iimol/l (mean(SEM),plasma nitrateconcentration was 17-9(2.4)

G M McKnight

Papers

Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans.

Dietary nitrate in man: friend or foe?

Plasma nitrate concentration in infective gastroenteritis and inflammatory bowel disease

Chemical synthesis ofnitric oxide inthestomach fromdietary nitrate inhumans