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

Poulsen S, Errboe M, Hovgaard O, Worthington HW. Potassium nitrate toothpaste for dentine hypersensitivity. Cochrane Database Syst Rev. 2001;(2):CD001476. doi: 10.1002/14651858.CD001476. Update in: Cochrane Database Syst Rev. 2006;(3):CD001476. 

Abstract. Background: Dentine hypersensitivity may be defined as the pain arising from exposed dentine, typically in response to external stimuli, and which cannot be explained by any other form of dental disease. Many treatment regimes have been recommended over the years, and in recent years particular attention has been focused on toothpastes containing potassium nitrate. Objectives: To compare the effectiveness of potassium nitrate containing toothpastes with placebo toothpastes in reducing dentine hypersensitivity. Search strategy: The following databases were cross searched via the database host DIALOG: MEDLINE, EMBASE, ELSEVIER BIOBASE, BIOSIS PREVIEWS, CAB HEALTH, SCI SEARCH, CURRENT CONTENTS until 1 April 2000. The specialised Cochrane Oral Health Group Trials Register was also searched. Bibliographies of clinical studies and reviews identified in the electronic search were checked for studies published outside the electronically searched journals. Selection criteria: Randomised clinical trials (RCTs) in which the effect on dentine hypersensitivity of potassium nitrate toothpastes were tested against non-potassium nitrate containing placebo toothpastes. Data collection and analysis: Two of the reviewers independently recorded the results of the included trials using a specially designed chart. Sensitivity was assessed by using thermal, tactile, air blast, and subjective methods. The quality of all RCTs, that fulfilled the inclusion criteria, was acceptable with Jadad scores ranging from 3 to 4 (Jadad 1998). Main results: Out of the eight studies that initially fulfilled the criteria to be included in the review, four studies did not present mean and standard deviations and could thus not be included in the meta-analysis. Three of these did not show an effect on any of the measurements of dentine hypersensitivity, while one did. Four studies were included in the meta-analysis which showed statistically significant effect of potassium nitrate toothpaste on air blast and tactile sensitivity, e.g. the meta analysis of air blast sensitivity showed a standardized mean difference in sensitivity score of -1.51 (95% CI: -2.09 to -0.94) in favour of treatment. The subjective assessment failed to show a significant effect at the six to eight week assessment.

Chazelas E, Pierre F, Druesne-Pecollo N, Esseddik Y, Szabo de Edelenyi F, Agaesse C, De Sa A, Lutchia R, Gigandet S, Srour B, Debras C, Huybrechts I, Julia C, Kesse-Guyot E, Allès B, Galan P, Hercberg S, Deschasaux-Tanguy M, Touvier M. Nitrites and nitrates from food additives and natural sources and cancer risk: results from the NutriNet-Santé cohort. Int J Epidemiol. 2022 Aug 10;51(4):1106-1119. doi: 10.1093/ije/dyac046.

Abstract. Background: Nitrates and nitrites occur naturally in water and soil. They are also used as food additives (preservatives) in processed meats. They could play a role in the carcinogenicity of processed meat. The objective was to investigate the relationship between nitrate and nitrite intakes (natural food, water and food additive sources) and cancer risk in a large prospective cohort with detailed dietary assessment. Methods: Overall, 101 056 adults from the French NutriNet-Santé cohort (2009-ongoing, median follow-up 6.7 years) were included. Nitrites/nitrates exposure was evaluated using repeated 24-h dietary records, linked to a comprehensive composition database and accounting for commercial names/brands of industrial products. Associations with cancer risk were assessed using multi-adjusted Cox hazard models. Results: In total, 3311 incident cancer cases were diagnosed. Compared with non-consumers, high consumers of food additive nitrates had higher breast cancer risk [hazard ratio (HR) = 1.24 (95% CI 1.03-1.48), P = 0.02], more specifically for potassium nitrate. High consumers of food additive nitrites had higher prostate cancer risk [HR = 1.58 (1.14-2.18), P = 0.008], specifically for sodium nitrite. Although similar HRs were observed for colorectal cancer for additive nitrites [HR = 1.22 (0.85-1.75)] and nitrates [HR = 1.26 (0.90-1.76)], no association was detected, maybe due to limited statistical power for this cancer location. No association was observed for natural sources.  Conclusion: Food additive nitrates and nitrites were positively associated with breast and prostate cancer risks, respectively. Although these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of these additives from the food industry. © The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.

Lintas C, Ibba P, Cundari E, De Siena E, Schiesser AP, Boniforti L, Massi O. Potassium nitrate and nitrosamine formation. Nutr Cancer. 1983;5(3-4):137-45. doi: 10.1080/01635588309513790.

Abstract. The influence of potassium nitrate on the formation of nitrosamines in salami was studied. Samples of salami were prepared, with and without the addition of potassium nitrate. Under the conditions of the experiment, potassium nitrate did not represent a source of either nitrite or nitrosamines. Independently of the presence of potassium nitrate in the sample formulation, the growth of bacterial flora reached a maximum in the first 20 days of the ripening process.

Bharadwaj L, Dhami K, Schneberger D, Stevens M, Renaud C, Ali A. Altered gene expression in human hepatoma HepG2 cells exposed to low-level 2,4-dichlorophenoxyacetic acid and potassium nitrate. Toxicol In Vitro. 2005 Aug;19(5):603-19. doi: 10.1016/j.tiv.2005.03.011.

Abstract. 2,4-dichlorophenoxyacetic acid (2,4-D) and nitrate are agricultural contaminants found in rural ground water. It is not known whether levels found in groundwater pose a human or environmental health risk, nor is the mechanism of toxicity at the molecular/cellular level understood. This study focused on determining whether 2,4-D or nitrate at environmentally realistic levels elicit gene expression changes in exposed cells. cDNA microarray technology was used to determine the impact of 2,4-D and nitrate in an in vitro model of exposure. Human hepatoma HepG2 cells were incubated with 2,4-D or nitrate alone for 24 h. Cell viability (neutral red assay) and proliferation (BrdU incorporation) were assessed following exposure. Total RNA from treated and control cells were isolated, reverse transcribed and reciprocal labelled with Cy3 or Cy5 dyes, and hybridized to a human cDNA microarray. The hybridized microarray chips were scanned, quantified and analyzed to identify genes affected by 2,4-D or nitrate exposure based on a two-fold increase or decrease in gene expression and reproducibility (affected in three or more treatments). Following filtering, normalization and hierarchical clustering initial data indicate that numerous genes were found to be commonly expressed in at least three or more treatments of 2,4-D or nitrate tested. The affected genes indicate that HepG2 cells respond to environmental, low-level exposure and produce a cellular response that is associated with alterations in the expression of many genes. The affected genes were characterized as stress response, cell cycle control, immunological and DNA repair genes. These findings serve to highlight new pathway(s) in which to further probe the effects of environmental levels of 2,4-D and nitrate.

Thompson C, Vanhatalo A, Kadach S, Wylie LJ, Fulford J, Ferguson SK, Blackwell JR, Bailey SJ, Jones AM. Discrete physiological effects of beetroot juice and potassium nitrate supplementation following 4-wk sprint interval training. J Appl Physiol (1985). 2018 Jun 1;124(6):1519-1528. doi: 10.1152/japplphysiol.00047.2018. Epub 2018 Mar 1. 

Abstract. The physiological and exercise performance adaptations to sprint interval training (SIT) may be modified by dietary nitrate ([Formula: see text]) supplementation. However, it is possible that different types of [Formula: see text] supplementation evoke divergent physiological and performance adaptations to SIT. The purpose of this study was to compare the effects of 4-wk SIT with and without concurrent dietary [Formula: see text] supplementation administered as either [Formula: see text]-rich beetroot juice (BR) or potassium [Formula: see text] (KNO3). Thirty recreationally active subjects completed a battery of exercise tests before and after a 4-wk intervention in which they were allocated to one of three groups: 1) SIT undertaken without dietary [Formula: see text] supplementation (SIT); 2) SIT accompanied by concurrent BR supplementation (SIT + BR); or 3) SIT accompanied by concurrent KNO3 supplementation (SIT + KNO3). During severe-intensity exercise, V̇o2peak and time to task failure were improved to a greater extent with SIT + BR than SIT and SIT + KNO3 ( P < 0.05). There was also a greater reduction in the accumulation of muscle lactate at 3 min of severe-intensity exercise in SIT + BR compared with SIT + KNO3 ( P < 0.05). Plasma [Formula: see text] concentration fell to a greater extent during severe-intensity exercise in SIT + BR compared with SIT and SIT + KNO3 ( P < 0.05). There were no differences between groups in the reduction in the muscle phosphocreatine recovery time constant from pre- to postintervention ( P > 0.05). These findings indicate that 4-wk SIT with concurrent BR supplementation results in greater exercise capacity adaptations compared with SIT alone and SIT with concurrent KNO3 supplementation. This may be the result of greater NO-mediated signaling in SIT + BR compared with SIT + KNO3. NEW & NOTEWORTHY We compared the influence of different forms of dietary nitrate supplementation on the physiological and performance adaptations to sprint interval training (SIT). Compared with SIT alone, supplementation with nitrate-rich beetroot juice, but not potassium [Formula: see text], enhanced some physiological adaptations to training.

Anderson OK, Martinez-Ferran M, Lorenzo-Calvo J, Jiménez SL, Pareja-Galeano H. Effects of Nitrate Supplementation on Muscle Strength and Mass: A Systematic Review. J Strength Cond Res. 2022 Dec 1;36(12):3562-3570. doi: 10.1519/JSC.0000000000004101.

Abstract.  -This systematic review examines the effect of dietary nitrate supplementation (SUP) on muscle strength and hypertrophy when combined with physical exercise. The databases PubMed, Web of Science, and MEDLINE were searched for full-text articles published between January 2000 and June 2020. For inclusion, studies had to report on the effects of SUP administered as acute or chronic doses together with a standardized exercise protocol on muscle strength and hypertrophy compared with placebo in healthy adults who were sedentary, physically active, or professional athletes. Twelve studies (1,571 subjects) were finally selected. In 5 studies, the SUP regime was acute, and in 7, it was chronic. SUP was nitrate-rich beetroot juice in 9 studies, a potassium nitrate capsule in 1, and increased dietary nitrate in 2. Ingested nitrate was 64-1,200 mg. Of the 12 studies, 6 observed an ergogenic effect of SUP compared with placebo. These findings indicate that muscle strength gains are possible provided the dose, format, frequency, period, and exercise test are appropriate. Best results were observed with a minimum acute dose of 400 mg of nitrate provided as beetroot juice/shot taken 2-2.5 hours before exercise involving low- and high-intensity muscle contractions. This SUP regime seems to improve muscle efficiency in terms of reduced phosphocreatine and energy costs (P-magnetic resonance spectroscopy) and improved time to exhaustion. Copyright © 2021 National Strength and Conditioning Association.

Bilczuk L, Gowin A, Ebertowska Z, Mach H. Zawartość azotanów i azotynów w całodziennych racjach pokarmowych dzieci wiejskich z rejonu Puław [Nitrate and nitrite levels in daily food rations of children from the rural Puławy regions]. Rocz Panstw Zakl Hig. 1991;42(2):139-47. 

Abstract.  In the region of Puławy where the operation of the Nitrogen-Compound Manufacturing Plant has lead to an increase in nitrogen compound emission to the environment, nitrate and nitrite contents in daily food rations of children were determined. Daily food rations of children aged 8-9 and 12-13 years were collected from individual farms in four villages situated in the vicinity of the Nitrogen Plant, as well as--for control--from individual farms in Janowiec, a village distant from this Plant. Nitrate and nitrite contents were assayed in 300 daily food rations taken in spring and autumn. Nitrate was reduced to nitrite on a cadmium column whereupon it was determined colorimetrically using sulphanilic acid and N-1-napthyl-ethylenediamine. It was found that in the group of younger children as many as 70%, on the average, of the examined food rations displayed nitrate contents exceeding the admissible levels. In the group of the 12-13 years old children, the percentage of daily food rations whose nitrate content exceeded the admissible level was lower, averaging ca. 30% of all rations examined. The percentage of the daily food rations in which the nitrite content was higher than admissible level was closely similar in both groups of children, averaging ca. 30% of all rations examined. Food rations collected in spring, as compared with those taken in autumn, contained significantly greater amount of nitrate. In both periods of studies, nitrate contents were greater in the food rations from the farms situated near the Nitrogen Plant than in the food rations from farms in Janowiec....

Hooper S, Seong J, Macdonald E, Claydon N, Hellin N, Barker ML, He T, West NX. A randomised in situ trial, measuring the anti-erosive properties of a stannous-containing sodium fluoride dentifrice compared with a sodium fluoride/potassium nitrate dentifrice. Int Dent J. 2014 Mar;64 Suppl 1(Suppl 1):35-42. doi: 10.1111/idj.12101. 

Abstract. Objectives: To determine if a stabilised, stannous-containing sodium fluoride dentifrice provides greater enamel protection in situ against intraoral dietary erosive challenges compared with a sodium fluoride/potassium nitrate dentifrice. Methods: A single-centre, investigator blind, randomised, supervised, two-treatment, non-brushing, four-period crossover in situ study was undertaken, with each test period being 15 days. Thirty-five healthy adult subjects were recruited to participate in the study, which included four erosive acid challenges per day. Subjects were randomised to product treatment, which included either: (1) a stannous-containing sodium fluoride dentifrice (Oral-B(®) Pro-Expert Sensitive) or (2) a sodium fluoride/potassium nitrate dentifrice (Sensodyne(®) Pronamel(®) ). Each study subject wore an intraoral appliance retaining two sterilised, polished human enamel samples for 6 hours/day. Subjects swished with an allocated dentifrice slurry twice a day and with 250 ml of orange juice for 10 minutes (25 ml/minute over a 10-minute period) four times per day. The primary and secondary outcomes for this study were enamel loss measured using contact profilometry at days 15 and 5, respectively, using parametric analysis methods. Results: At day 15, a 38% lower enamel loss (P < 0.0001) was observed, with estimated medians of 2.03 μm (SE 0.247) and 3.30 μm (SE 0.379), in favour of the stannous-containing dentifrice. At day 5, specimens treated with the stannous-containing sodium fluoride dentifrice demonstrated 25% less enamel loss than those treated with the sodium fluoride/potassium nitrate dentifrice. Treatment differences at day 5 were also statistically significant (P < 0.05), with estimated medians of 1.37 μm (SE 0.177) and 1.83 μm (SE 0.223), respectively. Conclusions: Results of this in situ study suggest the stabilised, stannous-containing sodium fluoride dentifrice could be used to provide significantly greater protection to enamel from erosive acid challenge compared with that provided by conventional fluoride-containing products. © 2014 FDI World Dental Federation.