Nitrate Intake Research Articles

Associations between Vegetable Nitrate Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review.

Consumption of nitrate-rich vegetables increases nitric oxide bioavailability, lowers blood pressure, and improves endothelial function. These effects could also translate into reduced cardiovascular disease (CVD) risk and mortality. This systematic review aimed to investigate the associations between habitual vegetable nitrate intake and CVD incidence and mortality. A secondary aim was to identify factors that moderate the relationship between vegetable nitrate intake and CVD incidence/mortality. Seven databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, CINAHL, and APA PsycINFO) were searched from inception to 13 February 2023. Observational studies quantifying vegetable nitrate intake in participants aged 18+ years through self-reported dietary exposure and assessing incidence or mortality from CVD overall, or individual CVD subtypes, were eligible. Five studies including a total of 63,155 participants were included. There was an inverse association between vegetable nitrate intake and most reported CVD outcomes. Reported risk reductions tended to plateau at moderate intake, suggesting a possible ceiling effect. The risk of bias across all studies was low. The results of this systematic review suggest a potential role for vegetable nitrate in reducing CVD risk and mortality. Further randomised controlled trials are now required to corroborate these findings.

The level of nitrate and nitrite in some fruits available in the local markets in District 7, Ho Chi Minh City, Vietnam

Nitrate and nitrite are main contaminants in fruits that must be controlled due to their potential adverse health effects on humans. The objectives of this study were to analyze levels of nitrate and nitrite in some selected fruits in local markets in District 7, Ho Chi Minh City, and to determine whether estimated dietary exposure to nitrate and nitrite poses a risk to human health. Mango, banana, tomato, and cucumber were collected and tested. Nitrate levels varied widely, ranging from 89 mg/kg to 1104 mg/kg across different fruits. Mango had the highest average nitrate level (588 mg/kg), while tomato had the lowest (109 mg/kg). Nitrite levels in fruits were significantly lower than nitrate levels, ranging from 0.090 mg/kg to 2.60 mg/kg. Mango had the highest average nitrite level (0.77 mg/kg), and cucumber had the lowest (0.01 mg/kg). The nitrate and nitrite health risk quotient (RQ) was within acceptable limits, indicating that nitrate and nitrite intake from fruit consumption poses no health risk to the local population. When the endogenous process of nitrate to nitrite transformation was considered, the EDI of nitrite increased significantly compared to the original calculation, but the result remained within the acceptable limit.

Can the dietary inorganic nitrate supplementation mitigate the vascular dysfunction in elderly with Alzheimer’s disease?

Aging and Alzheimer disease (AD) are both characterized by progressive reduction in nitric oxide bioavailability and endothelial function impairment. Promising studies on young healthy individuals underly the positive effect of dietary nitrate supplementation on endothelial function. However, the pharmacokinetics of the plasma nitrate and nitrite (PN) and the accompanying endothelial responsiveness following the oral nitrate ingestion in healthy elderly (HE) and patients with AD is not clear. Our hypothesis was that due to the reduction of nitric oxide bioavailability during aging and AD, an equal dose of oral nitrate (ON) would ameliorate the endothelial responsiveness more in the HE and even more in patients with AD in comparison to healthy young subjects (HY). Therefore, with the aim of investigating the pharmacokinetics of PN and the time-course endothelial responsiveness in response to a single dose ON, 10 HY (25±4 YRS), 10 HE (72±8 YRS) and 13 AD (73±7 YRS) were recruited. PN levels and endothelial responsiveness (single-passive leg movement (ΔPLM)) were measured in the recruited individuals prior to (T0) and hourly for 4 hours (T1, T2, T3, and T4) after: a) a single dose of ON; and b) a single dose of placebo. As expected at T0 both PN and ΔPLM were significantly reduced in the HE and even more reduced in the AD in comparison to the HY (all p<0.001). No changes in PN nor ΔPLM were detected in any group following placebo intake. PN increased significantly in all three groups at T1 (p<0.001) and constantly increased up to T4, but no differences were detected between time points T1 to T4 in any group. ΔPLM increased significantly in all three groups at T2, reaching highest values at T4 (p<0.001). However, AD exhibited significantly lower ΔPLM values at any time point compared to HY (p<0.0001) and HE (p<0.001). Significant correlation between PN and ΔPLM was found (p<0.001, R2=0.1654). Contrary to our hypothesis, the results of this study suggest that the PN pharmacokinetics following a single dose of ON is similar in HY, HE and AD. Moreover, the expected time-course amelioration of the endothelial responsiveness was reduced in the HE and even more reduced in the AD, suggesting that other factors, rather than the nitric oxide bioavailability, are playing a role in the age- and AD-related vascular dysfunction. Ricerca di Base 2017 - RBVR17XRSA - Effectiveness of exercise and nitrate supplementation on progression of dementia in patients with Alzheimer’s disease. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nitrate ingestion blunts the increase in blood pressure during cool air exposure: a double-blind, placebo-controlled, randomized, crossover trial.

Cold exposure increases blood pressure (BP) and salivary flow rate (SFR). Increased cold-induced SFR would be hypothesized to enhance oral nitrate delivery for reduction to nitrite by oral anaerobes and to subsequently elevate plasma [nitrite] and nitric oxide bioavailability. We tested the hypothesis that dietary nitrate supplementation would increase plasma [nitrite] and lower BP to a greater extent in cool compared with normothermic conditions. Twelve males attended the laboratory on four occasions. Baseline measurements were completed at 28°C. Subsequently, participants ingested 140 mL of concentrated nitrate-rich (BR; ∼13 mmol nitrate) or nitrate-depleted (PL) beetroot juice. Measurements were repeated over 3 h at either 28°C (Norm) or 20°C (Cool). Mean skin temperature was lowered compared with baseline in PL-Cool and BR-Cool. SFR was greater in BR-Norm, PL-Cool, and BR-Cool than PL-Norm. Plasma [nitrite] at 3 h was higher in BR-Cool (592 ± 239 nM) versus BR-Norm (410 ± 195 nM). Systolic BP (SBP) at 3 h was not different between PL-Norm (117 ± 6 mmHg) and BR-Norm (113 ± 9 mmHg). SBP increased above baseline at 1, 2, and 3 h in PL-Cool but not BR-Cool. These results suggest that BR consumption is more effective at increasing plasma [nitrite] in cool compared with normothermic conditions and blunts the rise in BP following acute cool air exposure, which might have implications for attenuating the increased cardiovascular strain in the cold.NEW & NOTEWORTHY Compared with normothermic conditions, acute nitrate ingestion increased plasma [nitrite], a substrate for oxygen-independent nitric oxide generation, to a greater extent during cool air exposure. Systolic blood pressure was increased during cool air exposure in the placebo condition with this cool-induced blood pressure increase attenuated after acute nitrate ingestion. These findings improve our understanding of environmental factors that influence nitrate metabolism and the efficacy of nitrate supplementation to lower blood pressure.

The risk of gastrointestinal cancer and nitrate intake due to vegetable consumption: A case-control study in Minab, Iran

The risk of gastrointestinal cancer and nitrate intake due to vegetable consumption: A case-control study in Minab, Iran

Exploring the Impact of Alternative Sources of Dietary Nitrate Supplementation on Exercise Performance.

An increase in the level of nitric oxide (NO) plays a key role in regulating the human cardiovascular system (lowering blood pressure, improving blood flow), glycemic control in type 2 diabetes, and may help enhance exercise capacity in healthy individuals (including athletes). This molecule is formed by endogenous enzymatic synthesis and the intake of inorganic nitrate (NO3-) from dietary sources. Although one of the most well-known natural sources of NO3- in the daily diet is beetroot (Beta vulgaris), this review also explores other plant sources of NO3- with comparable concentrations that could serve as ergogenic aids, supporting exercise performance or recovery in healthy individuals. The results of the analysis demonstrate that red spinach (Amaranthus spp.) and green spinach (Spinacia oleracea) are alternative natural sources rich in dietary NO3-. The outcomes of the collected studies showed that consumption of selected alternative sources of inorganic NO3- could support physical condition. Red spinach and green spinach have been shown to improve exercise performance or accelerate recovery after physical exertion in healthy subjects (including athletes).

Abstract P199: Oral Microbiome Potentially Modifies the Cardiometabolic Benefits of Nitrate Consumption: Results From the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS)

Background: Dietary nitrate consumption is associated with cardiometabolic health in many but not all studies. The enterosalivary nitrate-nitrite-nitric oxide (NO 3 - NO 2 - NO) pathway requires the oral microbiome for NO production (a signaling molecule beneficial to cardiometabolic health) following nitrate intake. We hypothesize that the oral microbiome modifies the cardiometabolic benefits of nitrate intake. Methods: We analyzed cross-sectional data from 657 ORGINS participants. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic biomarker (systolic and diastolic blood pressure, HbA1C, glucose, insulin, and HOMA-IR) Z-scores were averaged to form a cardiometabolic Z-score (CMZ). Adjusted multivariable linear models regressed CMZ and individual Z-scores on nitrate intake tertiles. Results: Participants were mean age 31±9, 72% female, 31% White, 14% Black, and 28% Hispanic. Mean nitrate intake was 189±171 mg/day. Higher nitrate intake was significantly associated with lower CMZ, glucose, insulin, and HOMA-IR. Mean CMZ(SE) across dietary nitrate tertiles were 0.53(0.30), 0.35(0.31), and -0.11(0.30), p for trend=0.04; findings were attenuated after adjustment for AHEI (p for trend=0.12). In subgroup analysis by MINES level, higher nitrate intake was only associated with lower cardiometabolic biomarker levels among participants with a <median MINES even after AHEI adjustment (Table). Conclusion: Higher dietary nitrate intake was associated with lower cardiometabolic risk biomarker levels only among those with reduced potential for oral microbiome-dependent NO generation.

Maternal use of nitrosatable drugs during pregnancy and adult male reproductive health: A population-based cohort study.

Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite. We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated. We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias. In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sensitive subpopulations were detected. The results suggest that maternal use of nitrosatable drugs does not have a harmful influence on the male fecundity of the offspring.

Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation.

SARS-CoV-2 induces a hyperinflammatory reaction due to the excessive release of cytokines during the immune response. The bacterial endotoxin lipopolysaccharide (LPS) contributes to the low-grade inflammation associated with the metabolic syndrome, enhancing the hyperinflammatory reaction induced by the SARS-CoV-2 infection. The intake of sodium nitrate, a precursor of nitrite and nitric oxide, influences the antioxidant and pro-inflammatory gene expression profile after immune stimulation with LPS in peripheral blood mononuclear cells from metabolic syndrome patients. We aimed to assess the inflammatory and antioxidant responses of immune cells from metabolic syndrome patients to exposure to the SARS-CoV-2 spike protein (S protein) together with LPS and the effect of nitrite in these responses. Whole blood samples obtained from six metabolic syndrome patients were cultured for 16 h at 37 °C with four different media: control medium, control medium plus LPS (100 ng/mL), control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL), and control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL) plus nitrite (5 µM). Immune stimulation with the LPS/S protein enhanced nitrate biosynthesis from nitrite oxidation and probably from additional organic precursors. In vitro incubations with the LPS/S protein enhanced the expression and/or release of pro-inflammatory TNFα, IL-6, IL-1β, and TLR4, as well as the expression of the anti-inflammatory IL-1ra and IL-10 and antioxidant enzymes. Nitrite attenuated the pro- and anti-inflammatory response induced by the S protein without interfering with the activation of TLR4 and antioxidant enzyme expression, raising the possibility that nitrite could have potential as a coadjutant in the treatment of COVID-19.

Groundwater Contamination with Nitrate and Human Health Risk Assessment of North East Alluvial Plains of Bihar, India

Groundwater is natural resources which supplies almost half of all drinking water in the world and plays a key role in food production. Consuming water containing high nitrate concentration have immediate effect on infant and could cause the risk of diseases Methemoglobinemia in which blood lacks the ability to carry sufficient oxygen to the individual body cells. As difference in nitrate concentration in water, made it important to study the undesirable effect of it. In rural areas, groundwater contamination is a problem related to the excessive use of chemical fertilizers by local farmers. Shallow groundwater plays a vital role in water use and the yield of Maize. Nitrogen application significantly affects crop uptake and utilization of water from irrigation, but little is known about groundwater use. Farmers are applying nitrogen on an average 278 kg/ha in Kharif maize, which is about 131.72% more than the RDN of Kharif maize i.e. 120 KgN/ha. The mean value of N application by farmers ranges from 251-323 kg/ha. The Maximum rate of N application was observed in Khagaria (323 kg N/ha) followed by Madhepura (275.08 kg N/ha) and minimum in case of Saharsa district (251.16 kg N/ha). The application rate of nitrogenous fertilizer, varying from 109.25% to 169.16% over the RDN, resulting in NO3- leaching. The groundwater and surfacewater from 12 villages was collected and various quality parameters were analysed. The nitrate in ground water varied (1.87- 6.19 mg/L) and surface water (1.87 – 3.84 mg/L) being maximum concentration of nitrate in Madhepura district. The present study on nitrate leaching in soil, its level of contamination in ground water and human health risk assessment by chronic daily intake of nitrate and Hazard Quotient (H.Q) values in the study area of Khagaria, Saharsa, Madhepura and Supaul has been carried out in the eastern alluvial region of Bihar.

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

The 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. In 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. In 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. Participants 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.

The association of dietary nitrates/nitrites intake and the gut microbial metabolite trimethylamine N-oxide and kynurenine in adults: a population-based study.

Dietary nitrate and nitrite may affect the gut microbiota and its metabolites, such as trimethylamine N-oxide (TMAO) and kynurenine (KYN). However, this association and the exact mechanism are still unclear. Therefore, this study aimed to assess the association between dietary consumption of nitrite and nitrate on TMAO and KYN levels in adults. This cross-sectional study was employed on a subsample baseline phase of the Tehran University of Medical Sciences (TUMS) Employee's Cohort Study (TEC). A total of 250 adults aged 18 years or older were included in the current analysis. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ), and dietary intakes of nitrite and nitrate were estimated using the FFQ with 144 items. Serum profiles and TMAO and KYN were measured using a standard protocol. The findings of this study demonstrate a significant association between the intake of animal sources of nitrate and nitrite and the likelihood of having elevated levels of TMAO and KYN. Specifically, after adjustment, individuals with the highest intake adherence to nitrates from animal sources exhibited increased odds of having the highest level of TMAO (≥51.02 pg/ml) (OR = 1.51, 95% CI = 0.59-3.88, P = 0.03) and KYN (≥417.41 pg/ml) (OR = 1.75, 95% CI = 0.73-4.17, P = 0.02). Additionally, subjects with the highest animal intake from nitrite sources have 1.73 and 1.45 times higher odds of having the highest levels of TMAO and KYN. These results emphasize the potential implications of animal-derived nitrate and nitrite consumption on the levels of TMAO and KYN. The present evidence indicates that a high level of nitrate and nitrite intake from animal sources can increase the odds of high levels of TMAO and KYN. Further studies suggest that we should better evaluate and understand this association.

Public health risk associated with the quality of drinking water and food, and the incidence of colorectal cancer

Aim to assess the public health risk associated with the quality of drinking water and food in areas with different levels of incidence of colorectal cancer.
 Material and methods. An assessment was made of the carcinogenic risk and the risk of developing general toxic effects due to the intake of xenobiotics with food and drinking water in areas that differ in the incidence of colorectal cancer. To assess the risk, the results of laboratory studies performed as part of the social and hygienic monitoring for the period 2014-2021 were used.
 Results. Priority pollutants (plumbum, arsenic, cadmium, hexachloran, polychlorinated biphenyls) that make the greatest contribution to the carcinogenic risk have been identified. The range of total carcinogenic risk, depending on arsenic compounds, varies in the Arsky district from acceptable to high (from 4.98E-05 to 2.70E-03), in Drozhzhanovsky - from acceptable to alarming (from 6.81E-05 to 2.02E- 04); in Aznakaevsky - from alarming to high (from 1.99E-04 to 2.21E-03). In the Kamsko-Ustyinsky district, the risk is assessed as alarming (from 2.15E-04 to 4.13E-04), in Yutazinsky as high (from 2.91E-03 to 3.39E-03). The total hazard index caused by the intake of nitrates with food and drinking water varies from the minimum in the Arsky district (HI=0.31) to the alarming one in the Kamsko-Ustyinsky district (HI=3.13). A correlation was established between the content of nitrates in drinking water and the incidence of cancer of the rectum, rectosigmoid junction and anus (r=0.587; p=0.002133). The risk of developing non-carcinogenic effects on the part of the gastrointestinal tract, due to the natural characteristics of drinking water sources, is assessed as acceptable in all areas.
 Conclusion. In areas with an increased incidence of colorectal cancer, there are higher levels of carcinogenic health risk due to the intake of xenobiotics with food and drinking water (from alarming to high).

Serum levels of trimethylamine N-oxide and kynurenine novel biomarkers are associated with adult metabolic syndrome and its components: a case-control study from the TEC cohort.

Epidemiologic research suggests that gut microbiota alteration (dysbiosis) may play a role in the pathogenesis of metabolic syndrome (MetS). Dysbiosis can influence Trimethylamine N-oxide (TMAO) a gut microbiota-derived metabolite, as well as kynurenine pathways (KP), which are known as a new marker for an early predictor of chronic diseases. Hence, the current study aimed to investigate the association between KYN and TMAO with MetS and its components. This case-control study was conducted on 250 adults aged 18 years or over of Tehran University of Medical Sciences (TUMS) Employee's Cohort study (TEC) in the baseline phase. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ) and dietary intakes of nitrite and nitrate were estimated using FFQ with 144 items. MetS was defined according to the NCEP ATP criteria. Serum profiles TMAO and KYN were measured by standard protocol. The mean level of TMAO and KYN in subjects with MetS was 51.49 pg/mL and 417.56 nmol/l. High levels of TMAO (≥30.39 pg/mL) with MetS were directly correlated, after adjusting for confounding factors, the odds of MetS in individuals 2.37 times increased (OR: 2.37, 95% CI: 1.31-4.28, P-value = 0.004), also, high levels of KYN (≥297.18 nmol/L) increased odds of Mets+ 1.48 times, which is statistically significant (OR: 1.48, 95% CI: 0.83-2.63, P-value = 0.04). High levels of TMAO compared with the reference group increased the odds of hypertriglyceridemia and low HDL in crude and adjusted models (P < 0.05). Additionally, there was a statistically significant high level of KYN increased odds of abdominal obesity (P < 0.05). Our study revealed a positive association between serum TMAO and KYN levels and MetS and some of its components. For underlying mechanisms and possible clinical implications of the differences. Prospective studies in healthy individuals are necessary.

Dietary nitrate intake and association with markers of cardiometabolic risk in Iranian female adolescents.

Dietary nitrates are thought to confer several cardiometabolic health benefits, including improvements in blood pressure and the plasma lipid profile. However, existing data from Iran is conflicting and there is a dearth of literature focusing on non-adult populations. A total of 988 adolescent girls were recruited from schools in different areas of Mashhad and Sabzevar, Iran. Dietary nitrate intake was assessed using a food frequency questionnaire and participants were categorized into quartiles based on this. Differences in participant characteristics between quartiles were assessed using one-way ANOVA and associations between total nitrate intake, nitrate intake from vegetables and cardiometabolic risk markers (blood lipid profile, fasting blood glucose, systolic and diastolic blood pressure) were assessed using linear regression. Nitrate intake from vegetables was positively correlated with triglycerides, even after adjusting for several variables (β = 0.086, 95% CI = 0.002-0.097; P = 0.043). Total nitrate intake was also significantly positively associated with serum triglycerides (β = 0.097, 95% CI = 0.010-0.084; P = 0.012); however, this relationship disappeared after adjusting for several variables. Significant interaction effects were observed between total nitrate intake, nitrate intake from vegetables, and vitamin C upon triglycerides (P < 0.01). No significant relationships were found between total nitrate intake, nitrate intake from vegetables, and other cardiometabolic risk markers. Our findings suggest there may be neutral or possibly detrimental cardiovascular effects of dietary nitrate and/or vitamin C intake which are not in agreement with contemporary literature and warrant further investigation.

Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study

BackgroundNitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD).ObjectivesWe investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation.MethodsWe performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993−1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999−2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake.ResultsWe identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C <median (T3 vs. T1 HR: 2.26, 95%CI: 1.05, 4.86) and with heme iron ≥median (T3 vs. T1 HR: 1.73, 95%CI: 0.89, 3.39).SignificanceESRD incidence was associated with dietary nitrate/nitrite from processed meat among all study participants and with total dietary nitrite among participants with lower vitamin C or higher heme iron intake.Impact statementThere are few well-established environmental risk factors for end-stage renal disease (ESRD), a worldwide public health challenge. Ingestion of nitrate and nitrite, which may lead to endogenous formation of carcinogenic N-nitroso compounds, has been linked to some cancers and chronic diseases. We investigated these exposures in relation to ESRD in an agricultural cohort. ESRD incidence was associated with dietary nitrate/nitrite from processed meat and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. This study provides preliminary evidence that points to dietary nitrite and possibly dietary nitrate intake as a potential contributor to ESRD.

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment (P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria (P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

Beet supplementation mitigates post-exercise inflammation.

This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive cycling in 20 male and female cyclists. A multi-omics approach was used that included untargeted proteomics and a targeted oxylipin panel. A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 2.25 h cycling bout at close to 70%VO2max. The BEET supplement provided 212 mg of nitrates per day, 200 mg caffeine from green tea extract, 44 mg vitamin C from Camu Camu berry, B-vitamins from quinoa sprouts (40% Daily Value for thiamin, riboflavin, niacin, and vitamin B6), and 2.5 g of a mushroom blend containing Cordyceps sinensis and Inonotus obliquus. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5 h-, 3 h-, and 24 h-post-exercise. The 2.25 h cycling bout increased plasma levels of 41 of 67 oxylipins detected. BEET supplementation significantly increased plasma nitrate (NO3 -) and nitrite (NO2 -) (sum, NO3 - + NO2 -) concentrations (interaction effect, p < 0.001) and two anti-inflammatory oxylipins [18-hydroxyeicosapentaenoic acid (18-HEPE) and 4-hydroxy-docosahexanoic acid (4-HDoHE)]. The untargeted proteomics analysis identified 616 proteins (458 across all times points), and 2-way ANOVA revealed a cluster of 45 proteins that were decreased and a cluster of 21 that were increased in the BEET versus PL trials. Functional enrichment supported significant BEET-related reductions in inflammation-related proteins including several proteins related to complement activation, the acute phase response, and immune cell adhesion, migration, and differentiation. Intake of a BEET-based supplement during a 2-week period was linked to higher plasma levels of NO3 - + NO2 -, elevated post-exercise levels of two anti-inflammatory oxylipins, and a significant decrease in a cluster of proteins involved in complement activation and inflammation. These data support that 2-weeks intake of nitrate from a mixed beet-based supplement moderated protein biomarkers of exercise-induced inflammation in athletes.

Nitrate Contamination of Groundwater in Selected Industrial and Non Industrial Sites, Coimbatore District, Tamil Nadu: Exposure and Health Risk Assessment

Groundwater resources are essential for sustaining human health, agricultural productivity, and industrial growth. In recent years, anthropogenic influences have caused a sharp decline in ground water quality, which is also having an impact on human health in many parts of India. It is crucial to analyze the risk of contamination to human health and the quality of the water supply. Coimbatore is one of the rapidly growing industrial areas in South India. The industrial areas of ground water have a significant impact on ground water quality due to anthropogenic activities such as discharge of Industrial waste, chemicals and pollutants into the ground which make water unsuitable for human and industrial use. Nitrate is the emerging contaminant which can cause a deadly disease methehemoglobinemia. Hence the present study is focused to analyze the ground water of selected industrial and non industrial sites of Coimbatore city. Nitrate concentration ranged from 32.90 to 88.13 mg/l in the samples industrial and non-industrial sites, and over 37% of both the sites had nitrate levels that above the Bureau of Indian Standards’ and WHO’s acceptable limits (45 mg/l and 50 mg/l, respectively). The USEPA human health risk assessment tool was used to examine the potential health hazards of increased nitrate intake for both adults and children.

Plant but not animal sourced nitrate intake is associated with lower dementia-related mortality in the Australian Diabetes, Obesity, and Lifestyle Study.

Dietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link. To investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status. This study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors. Over 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes. Encouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.