Compendium of the most significant studies with reference to properties, intake, effects.

Clements WT, Lee SR, Bloomer RJ. Nitrate ingestion: a review of the health and physical performance effects. Nutrients. 2014 Nov 18;6(11):5224-64. doi: 10.3390/nu6115224.

Abstract. This paper provides an overview of the current literature and scientific evidence surrounding inorganic nitrate (NO3-) supplementation and its potential for improving human health and physical performance. As indicative of the ever-expanding organic and natural food consumer market, athletes and health enthusiasts alike are constantly searching for ingredient-specific "super foods" and dietary supplements capable of eliciting health and performance benefits. Evidence suggests that NO3- is the viable active component within beetroot juice (BRJ) and other vegetables, responsible for health-promoting and ergogenic effects. Indeed, multiple studies support NO3- supplementation as an effective method to improve exercise performance. NO3- supplementation (either as BRJ or sodium nitrate [NaNO3-]) has also demonstrated modest benefits pertaining to cardiovascular health, such as reducing blood pressure (BP), enhancing blood flow, and elevating the driving pressure of O2 in the microcirculation to areas of hypoxia or exercising tissue. These findings are important to cardiovascular medicine/exercise physiology and suggest a possible role for NO3- supplementation: (1) as a low-cost prevention and treatment intervention for patients suffering from blood flow disorders; and (2) an effective, natural ergogenic aid for athletes. Benefits have been noted following a single bolus, as well as daily supplementation of NO3-. While results are promising, additional research is needed to determine the impact of NO3- supplementation on anaerobic exercise performance, to identify principle relationships between isolated nitrate and other ingredients found in nitrate-rich vegetables (e.g., vitamin C, polyphenols, fatty acids, thiocyanate), to explore the specific dose-response relationships needed to elicit health and ergogenic benefits, to prolong the supplementation period beyond a relatively short period (i.e., >15 days), to determine if more robust effects can be observed with longer-term treatment, and to fully examine the safety of chronic NO3- supplementation, as this continues to be a concern of some.

Lin JK, Lai CC. Effects of lactobacillus, antacids and antibiotics on the levels of nitrite in the gastro-intestinal tracts of rats fed sodium nitrate. Food Chem Toxicol. 1982 Apr;20(2):197-204. doi: 10.1016/s0278-6915(82)80248-2.

Abstract. No nitrite was detected in the tissues or contents of the gastro-intestinal tracts of normal rats but after 2 wk on a diet containing 0 . 5% sodium nitrate the levels of nitrite in the stomach, small intestine and large intestine contents were 0 . 83%, 1 . 64-2 . 07 and 0 . 83 micrograms/g of contents respectively. Concurrent administration of 2% Lactobacillus preparation and 0 . 5% sodium nitrate in the diet for 2 wk further increased the nitrite levels in the intestines and slightly increased the level in the stomach. The elevation of nitrite levels induced by sodium nitrate administration was potentiated considerably by combined treatment with sodium bicarbonate and hetacillin producing nitrite levels of 3 . 16, 2 . 93-5 . 18 and 1 . 96-2 . 34 micrograms/g of the contents of the stomach, small intestine and large intestine respectively. Like hetacillin, minomycin and thiamphenicol also potentiated the nitrite production whereas amikacin (another antibiotic) strongly inhibited the formation of nitrite in the stomach. The different effects of the antibiotics may be due to their selective activities on the various microbes. The results indicate that the levels of nitrite in the gastro-intestinal tract are regulated by the level of nitrate intake, the population of microflora and the gastric pH. The safety of combined medication with antacids, antibiotics and Lactobacillus preparations in man deserves further investigation.

Bescos, R., Ferrer-Roca, V., Galilea, P.A., Roig, A., Drobnic, F., Sureda, A., Martorell, M., Cordova, A., Tur, J.A. and Pons, A., 2012. Sodium nitrate supplementation does not enhance performance of endurance athletes. Medicine and science in sports and exercise, 44(12), pp.2400-2409.

Abstract. Purpose. Supplementation with inorganic nitrate has been suggested to be an ergogenic aid for athletes as nitric oxide donor. The purpose of this study was to determine whether ingestion of inorganic sodium nitrate benefits well-trained athletes performing a 40-min exercise test in laboratory conditions. In addition, we investigated the effect of this supplement on plasma levels of endothelin-1 (ET-1) and in nitrated proteins. Methods Thirteen trained athletes participated in this randomized, double-blind, crossover study. They performed a 40-min cycle ergometer distance-trial test after two 3-d periods of dietary supplementation with sodium nitrate (10 mg·kg of body mass) or placebo. Results. Concentration of plasma nitrate (256 ± 35 μM) and nitrite (334 ± 86 nM) increased significantly (P < 0.05) after nitrate supplementation compared with placebo (nitrate: 44 ± 11 μM; nitrite: 187 ± 43 nM). In terms of exercise performance, there were no differences in either the mean distance (nitrate: 26.4 ± 1.1 km; placebo: 26.3 ± 1.2 km; P = 0.61) or mean power output (nitrate: 258 ± 28 W; placebo: 257 ± 28 W; P = 0.89) between treatments. Plasma ET-1 increased significantly (P < 0.05) just after exercise in nitrate (4.0 ± 0.8 pg·mL) and placebo (2.4 ± 0.4 pg·mL) conditions. This increase was significantly greater (P < 0.05) in the nitrate group. Levels of nitrated proteins did not differ between treatments (nitrate: preexercise, 91% ± 23%; postexercise, 81% ± 23%; placebo: preexercise, 95% ± 20%; postexercise, 99% ± 19%). Conclusion. Sodium nitrate supplementation did not improve a 40-min distance-trial performance in endurance athletes. In addition, concentration of plasma ET-1 increased significantly after exercise after supplementation with sodium nitrate.

Katan, M. B. (2009). Nitrate in foods: harmful or healthy?. The American journal of clinical nutrition, 90(1), 11-12.

Abstract. Nitrate and nitrite are considered hazardous, and there are legal limits to their concentration in food and drinking water. Nitrate from fertilizer accumulates in vegetables and fruit, and large-scale livestock production yields huge amounts of manure rich in nitrate that seeps into groundwater. Therefore, keeping nitrate concentrations below legal limits is a struggle for farmers. In this issue of the Journal, Hord et al (1) challenge these limits. Other authors have already pointed out that the evidence for adverse effects of nitrate is inconsistent and that nitrate may actually be beneficial (2, 3). Hord et al (1) go one step further: they claim that nitrate and nitrite should be considered as nutrients....

Hord NG, Tang Y, Bryan NS. Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr. 2009 Jul;90(1):1-10. doi: 10.3945/ajcn.2008.27131.

Abstract. The presence of nitrates and nitrites in food is associated with an increased risk of gastrointestinal cancer and, in infants, methemoglobinemia. Despite the physiologic roles for nitrate and nitrite in vascular and immune function, consideration of food sources of nitrates and nitrites as healthful dietary components has received little attention. Approximately 80% of dietary nitrates are derived from vegetable consumption; sources of nitrites include vegetables, fruit, and processed meats. Nitrites are produced endogenously through the oxidation of nitric oxide and through a reduction of nitrate by commensal bacteria in the mouth and gastrointestinal tract. As such, the dietary provision of nitrates and nitrites from vegetables and fruit may contribute to the blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) diet. We quantified nitrate and nitrite concentrations by HPLC in a convenience sample of foods. Incorporating these values into 2 hypothetical dietary patterns that emphasize high-nitrate or low-nitrate vegetable and fruit choices based on the DASH diet, we found that nitrate concentrations in these 2 patterns vary from 174 to 1222 mg. The hypothetical high-nitrate DASH diet pattern exceeds the World Health Organization's Acceptable Daily Intake for nitrate by 550% for a 60-kg adult. These data call into question the rationale for recommendations to limit nitrate and nitrite consumption from plant foods; a comprehensive reevaluation of the health effects of food sources of nitrates and nitrites is appropriate. The strength of the evidence linking the consumption of nitrate- and nitrite-containing plant foods to beneficial health effects supports the consideration of these compounds as nutrients.

Butler AR, Feelisch M. Therapeutic uses of inorganic nitrite and nitrate: from the past to the future. Circulation. 2008 Apr 22;117(16):2151-9. doi: 10.1161/CIRCULATIONAHA.107.753814. 

Abstract. Potential carcinogenic effects, blue baby syndrome, and occasional intoxications caused by nitrite, as well as the suspected health risks related to fertilizer overuse, contributed to the negative image that inorganic nitrite and nitrate have had for decades. Recent experimental studies related to the molecular interaction between nitrite and heme proteins in blood and tissues, the potential role of nitrite in hypoxic vasodilatation, and an unexpected protective action of nitrite against ischemia/reperfusion injury, however, paint a different picture and have led to a renewed interest in the physiological and pharmacological properties of nitrite and nitrate. The range of effects reported suggests that these simple oxyanions of nitrogen have a much richer profile of biological actions than hitherto assumed, and several efforts are currently underway to investigate possible beneficial effects in the clinical arena. We provide here a brief historical account of the medical uses of nitrite and nitrate over the centuries that may serve as a basis for a careful reassessment of the health implications of their exposure and intake and may inform investigations into their therapeutic potential in the future.

Zetterquist W, Pedroletti C, Lundberg JO, Alving K. Salivary contribution to exhaled nitric oxide. Eur Respir J. 1999 Feb;13(2):327-33. doi: 10.1034/j.1399-3003.1999.13b18.x. 

Abstract. Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of exhaled NO. Ten healthy subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with a chemiluminescence technique up to 3 h after the ingestion. Measurements of exhaled NO were performed with a single-breath procedure, standardized to a 20-s exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values of NO were registered as NO release rate (pmol x s(-1)) during the plateau of exhalation. Exhaled NO increased steadily over time after nitrate load and a maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p<0.01), whereas no increase was detected in nasal NO levels. Salivary nitrite concentrations increased in parallel; at 120 min there was a four-fold increase compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p<0.05). The nitrite-reducing conditions in the oral cavity were also manipulated by the use of different mouthwash procedures. The antibacterial agent chlorhexidine acetate (0.2%) decreased NO release by almost 50% (p<0.01) 90 min after nitrate loading and reduced the preload control levels by close to 30% (p<0.05). Sodium bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent than chlorhexidine acetate. In conclusion, salivary nitric oxide formation contributes to nitric oxide in exhaled air and a large intake of nitrate-rich foods before the investigation might be misinterpreted as an elevated inflammatory activity in the airways. This potential source of error and the means for avoiding it should be considered in the development of a future standardized method for measurements of exhaled nitric oxide.