High Nitrate Diet Research Articles

Factors that Moderate the Effect of Nitrate Ingestion on Exercise Performance in Adults: A Systematic Review with Meta-Analyses and Meta-Regressions

To identify how variables such as exercise condition, supplementation strategy, participant characteristics and demographics, and practices that control oral microbiota diversity could modify the effect of inorganic nitrate ingestion (as nitrate salt supplements, beetroot juice, and nitrate-rich vegetables) on exercise performance, we conducted a systematic review with meta-analysis. Studies were identified in PubMed, Embase, and Cochrane databases. Eligibility criteria included randomized controlled trials assessing the effect of inorganic nitrate on exercise performance in healthy adults. To assess the variation in effect size, we used meta-regression models for continuous variables and subgroup analysis for categorical variables. A total of 123 studies were included in this meta-analysis, comprising 1705 participants. Nitrate was effective for improving exercise performance (standardized mean difference [SMD]: 0.101; 95% CI: 0.051, 0.151, P<0.001, I2=0%), although nitrate salts supplementation was not as effective (P=0.629) as ingestion via beetroot juice (P<0.001) or a high-nitrate diet (P=0.005). Practices that control oral microbiota diversity influenced the nitrate effect, with practices harmful to oral bacteria decreasing the ergogenic effect of nitrate. The ingestion of nitrate was most effective for exercise lasting between 2 and 10 min(P<0.001). An inverse dose-response relation between the fraction of inspired oxygen and the effect size (coefficient: -0.045, 95% CI: -0.085, -0.005, P=0.028) suggests that nitrate was more effective in increasingly hypoxic conditions. There was a dose-response relation for acute administration (P=0.049). The most effective acute dose was between 5 and 14.9 mmolprovided ≥150 minprior to exercise (P<0.001). An inverse dose-response for protocols≥2 d was observed (P=0.025), with the optimal dose between 5 and 9.9 mmol·d-1 (P<0.001). Nitrate, via beetroot juice or a high-nitrate diet, improved exercise performance, in particular, in sessions lasting between 2 and 10 min.Ingestion of 5-14.9 mmol⋅d-1 taken ≥150 minprior to exercise appears optimal for performance gains and athletes should be aware that practices controlling oral microbiota diversity may decrease the effect of nitrate.

Control of rat muscle nitrate levels after perturbation of steady state dietary nitrate intake

The roles of nitrate and nitrite ions as nitric oxide (NO) sources in mammals, complementing NOS enzymes, have recently been the focus of much research. We previously reported that rat skeletal muscle serves as a nitrate reservoir, with the amount of stored nitrate being highly dependent on dietary nitrate availability, as well as its synthesis by NOS1 enzymes and its subsequent utilization. We showed that at conditions of increased NO need, this nitrate reservoir is used in situ to generate nitrite and NO, at least in part via the nitrate reductase activity of xanthine oxidoreductase (XOR). We now further investigate the dynamics of nitrate/nitrite fluxes in rat skeletal muscle after first increasing nitrate levels in drinking water and then returning to the original intake level. Nitrate/nitrite levels were analyzed in liver, blood and several skeletal muscle samples, and expression of proteins involved in nitrate metabolism and transport were also measured. Increased nitrate supply elevated nitrate and nitrite levels in all measured tissues. Surprisingly, after high nitrate diet termination, levels of both ions in liver and all muscle samples first declined to lower levels than the original baseline. During the course of the overall experiment there was a gradual increase of XOR expression in muscle tissue, which likely led to enhanced nitrate to nitrite reduction. We also noted differences in basal levels of nitrate in the different types of muscles. These findings suggest complex control of muscle nitrate levels, perhaps with multiple processes to preserve its intracellular levels.

Correlation of Aerobic Exercise and High Nitrate Diet with Population of Eschericia Coli in the Digestive Tract of Liver Cirrhosis Individuals

Background: In liver cirrhosis, the population of E coli is increased. conditions such as reduced intestinal). Escherichia coli with 2 enzyme nitrate reductase (NRF and Nir) reduce nitrate to nitrite and subsequently converted to ammonia (99%) and nitric oxide (1%) in anaerobic condition. Regular aerobic exercise 2-3 times/week for 30 minutes resulted in increased 2,3-DPG which reduces the activity of E. coli to reduce nitrate to nitrite and ammonia, which only works on the anaerobic state. High Nitrate Diets lead to increased nitrate reducing bacteria such as E. coli resulting in the reduction of nitrate excess produce nitrite and ammonia in large quantities. Probiotic Lactobacillus spp. can suppress the growth of bacterial endotoxins and pathogens such as E. coli and other Enterobacteriaceae. This study aimed to determine the correlation of aerobic exercise and a high nitrate diet in gastrointestinal populations of Escherichia coli gastrointestinal tract in patient with liver cirrhosis.Method: This was a descriptive-experimental study in liver cirrhosis patients Child Pugh A/B in outpatient clinic Saiful Anwar Hospital in August 2015. Respondents were asked to fill out a questionnaire with information about the demographic data, the nitrate diet, aerobic exercise, other medical data and sanitation, and stool samples were taken for faecal culture. Eta Correlation statistical test was used to determine the correlation of aerobic exercise and a high nitrate diet high in population of E. coli. The significant difference are indicated by p 0.005.Results: A total of 36 patients diagnosed with liver cirrhosis Child Pugh A/B, 14 (39%) underwent aerobic exercise 3x /week, as many as 25 (70%) consume a high nitrate diet. There was a strong relationship between aerobic exercise and high nitrate diet with population of E. coli (Ƞ = 0.725; p 0.05).Conclusion: There was a strong relationship between aerobic exercise and high nitrate diet with a population of E. coli in liver cirrhosis. Giving probiotics in patients with liver cirrhosis suppressed the population of E. coli.

Vegetables with High-Nitrate Content Significantly Increase Plasma Nitrate and Nitrite Concentrations but Do Not Significantly Reduce Systolic Blood Pressure in Young Healthy Men

Aims: To investigate the effects of supplementation with high-nitrate and low-nitrate vegetables on plasma nitrate and nitrite concentrations, blood pressure and the oxygen demand of moderate-intensity exercise.&#x0D; Study Design: A randomized, cross-over design.&#x0D; Place and Duration of Study: Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, between January 2011 and March 2012.&#x0D; Methodology: 15 non-smoking, physically active healthy men (age 25 ± 6 years, BMI 24 ± 4 kg/m2) were randomized to receive a 2-week supply of high-nitrate or low-nitrate vegetables, with a 2-week ‘wash-out’ period in between. Clinic blood pressure, plasma nitrate and nitrite concentrations and physiological responses to moderate-intensity exercise tests were measured before and after each 2-week intervention. Nitrate intake was calculated using nutritional analysis of reported vegetables consumed.&#x0D; Results: Participants consumed significantly more dietary nitrate on the high-nitrate diet (417 ± 139 mg/day) than the low-nitrate diet (26 ± 11 mg/day). The high-nitrate diet supplied 5.5 mg nitrate/kg body weight, exceeding the Acceptable Daily Intake (ADI) of 3.7 mg nitrate/kg body weight. Supplementation with high-nitrate vegetables significantly increased plasma nitrate concentrations (baseline; 30 ± 20 µM, after high-nitrate vegetables; 129 ± 87 µM) and plasma nitrite concentrations (baseline; 119 ± 35 nM, after high-nitrate vegetables; 227 ± 89 nM) but did not significantly change systolic blood pressure or the physiological response to moderate exercise. There were significant correlations between diastolic blood pressure and plasma nitrite concentrations (low-nitrate diet; r = 0.63, high-nitrate diet, r = 0.56).&#x0D; Conclusion: Supplementation with high-nitrate vegetables above the ADI significantly increased plasma nitrate and nitrate concentrations but did not significantly reduce systolic blood pressure or the physiological response to moderate exercise. Plasma nitrite concentrations significantly correlated with diastolic blood pressure after high-nitrate and low-nitrate diets.

Effectiveness of dietary inorganic nitrate for lowering blood pressure in hypertensive adults: a systematic review.

The objective of this review was to evaluate the effectiveness of inorganic nitrate on blood pressure in hypertensive adults. Hypertension is associated with increased risk of morbidity and mortality in adults. Inorganic nitrate could be beneficial for lowering blood pressure and reducing cardiovascular disease risks. Evidence related to the treatment of hypertension through sources of inorganic nitrate has been presented. The review considered studies on adults aged 18 years and over, with blood pressure greater than 120/80 mmHg, undergoing interventions focusing on the effects of inorganic nitrate on blood pressure. Studies that included inorganic nitrate intake via dietary modification, in the form of a dietary supplement, and/or by the consumption of beetroot juice were considered. The comparator was no intervention of inorganic nitrate; different dosage, frequency, duration of inorganic nitrate; and other interventions that are administered to reduce and manage blood pressure. The primary outcomes were systolic and diastolic blood pressure effects. Experimental, quasi-experimental, analytical observational and pilot study designs were considered for inclusion. Databases were searched for published and unpublished studies, available in English, from January 2013 to January 2018. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute (JBI) and the methodological quality of included studies was considered to be moderate. Data were extracted using the JBI data extraction instrument. Data were presented in a narrative form due to the heterogeneity of included studies. Twelve papers were included in the systematic review with a total of 321 participants. Ten were randomized controlled trials and two were quasi-experimental studies. All participants had baseline blood pressures greater than 120/80 mmHg. Some studies included participants with comorbidities such as diabetes or heart failure with preserved ejection fraction. Inorganic nitrate was administered multiple ways throughout the studies including the following: beetroot juice, beetroot gel, nitric oxide lozenge, high nitrate diet, and raw and cooked beet juice. Doses and treatment intervals varied. Some studies included exercise as part of the intervention protocol.Meta-analysis was not conducted due to heterogeneity that existed within the studies. Blood pressure was measured in multiple settings by manual, digital or ambulatory means. The noted outcome patterns were as follows: no change in systolic blood pressure and diastolic blood pressure, decrease in systolic blood pressure and diastolic blood pressure, or decrease in systolic blood pressure with no change in diastolic blood pressure. Possible reasons for the diverse findings include the following: age, comorbidities, use of antihypertensives by participants; source and dose of nitrate; and intervention and follow-up time frames. There is insufficient evidence to support or refute the use of inorganic nitrate for any effect on blood pressure at this time. Therefore, there is no concrete base for the development of practice guidelines until stronger evidence becomes available. The gaps in the literature along with the study limitations identified necessitate the need for more research on inorganic nitrate and how it relates to blood pressure.

Effect of dietary nitrate on enteric methane emissions, production performance and rumen fermentation of dairy cows grazing kikuyu-dominant pasture during summer

Dietary nitrate supplementation is an effective methane (CH4) mitigation strategy in total mixed ration based diets fed to ruminants. To date, limited information is available on the effect of dietary nitrate on CH4 production from grazing dairy cows. Fifty-four multiparous Jersey cows were subjected to a randomised complete block design (blocked according to milk yield, days in milk and parity) to evaluate the effect of three dietary nitrate levels on enteric CH4 emissions and cow production performance. Additionally, six rumen-cannulated cows in a replicated 3 × 3 Latin square design were used in a rumen study. Dietary treatments consisted of concentrate fed at 5.4 kg of DM/cow per day containing one of three levels of dietary nitrate: 0 g (control), 11 g (low nitrate), and 23 g of nitrate/kg of dry matter (DM; high nitrate). Cows grazed late-summer pasture containing approximately 3 g of nitrate/kg of DM. Concentrates were formulated to be isonitrogenous, by substituting urea, and isoenergetic. Cows were gradually adapted to concentrates over a 3-wk period before the onset of a 57-d experimental period. Enteric CH4 emissions and total dry matter intake (DMI) from 11 cows per treatment were measured during one 6-d measurement period using the sulphur hexafluoride tracer gas technique. Individual pasture DMI was determined using TiO2 and indigestible neutral detergent fibre (NDF). Milk yield decreased by approximately 12% when feeding the high nitrate diet compared with the control and low nitrate diets. Although total DMI was unaffected by treatment, concentrate DMI decreased linearly (5.5–3.7 kg/d) while pasture DMI increased linearly (9.1–11.4 kg/d) with increasing dietary nitrate addition. Methane production (313–280 g/d), CH4 yield (21.8–18.7 g/kg of DMI) and CH4 energy per gross energy intake (6.9–5.9%) tended to decrease linearly with increasing dietary nitrate addition. Diurnal ruminal pH of the high nitrate group was greater, for selective periods after concentrate feeding, than the control and low nitrate groups. Spot sample ruminal pH (6.2–6.3) tended to increase while total volatile fatty acid (VFA) concentration (99.9–104 mM/L) increased quadratically with increasing dietary nitrate addition. Individual VFA concentrations were unaffected by treatment. Rate of NDF disappearance (2.4–2.8%/h) after 18 h of ruminal incubation tended to increase quadratically with increasing dietary nitrate addition. Dietary nitrate fed to grazing dairy cows tended to decrease CH4 emissions while improving the fibrolytic environment of the rumen. However, when feeding high levels of dietary nitrate a decrease in milk yield could be expected due to a decrease in concentrate DMI.

Yüksek Nitratlı Diyetle Beslenen Ankara Keçilerinde Tiroid Hormonları Üzerine Kükürt İlavesinin Etkileri

This study was to aimed for determination the effect of high dietary nitrate intake and inorganic sulphur supplementation on thyroids hormones in Angora goats. In this study, eighteen male Angora goats aged 14 months were divided into three groups ( n = 6): control group fed with a basal diet, nitrate group fed with a basal diet supplemented with 1500 ppm nitrate, and nitrate + sulfur group fed with a basal diet supplemented with 1500 ppm nitrate and 1.8% sodium sulfate. On days 45, 90, 135, and 180 of the study, the concentrations of the thyroid-stimulating hormone (TSH), total and free triiodothyronine (TT 3 and FT 3 ), and tetraiodothyronine (TT 4 and FT 4 ) were measured in the serum samples. On day 180, except for TT 4 , the serum TSH and total and free T 3 and free T 4 concentrations were higher (P<0.05) in the nitrate + sulfur group than in the control and nitrate groups. This study suggested that Angora goats could tolerate a feed containing 1500 ppm nitrate with respect to the thyroid hormones, and inorganic sulfur might serve as a natural source for alleviating the negative effects of the high-nitrate diet on the thyroid gland in a dose-dependent manner.

Effects of a Short-Term High-Nitrate Diet on Exercise Performance.

It has been reported that nitrate supplementation can improve exercise performance. Most of the studies have used either beetroot juice or sodium nitrate as a supplement; there is lack of data on the potential ergogenic benefits of an increased dietary nitrate intake from a diet based on fruits and vegetables. Our aim was to assess whether a high-nitrate diet increases nitric oxide bioavailability and to evaluate the effects of this nutritional intervention on exercise performance. Seven healthy male subjects participated in a randomized cross-over study. They were tested before and after 6 days of a high (HND) or control (CD) nitrate diet (~8.2 mmol∙day−1 or ~2.9 mmol∙day−1, respectively). Plasma nitrate and nitrite concentrations were significantly higher in HND (127 ± 64 µM and 350 ± 120 nM, respectively) compared to CD (23 ± 10 µM and 240 ± 100 nM, respectively). In HND (vs. CD) were observed: (a) a significant reduction of oxygen consumption during moderate-intensity constant work-rate cycling exercise (1.178 ± 0.141 vs. 1.269 ± 0.136 L·min−1); (b) a significantly higher total muscle work during fatiguing, intermittent sub-maximal isometric knee extension (357.3 ± 176.1 vs. 253.6 ± 149.0 Nm·s·kg−1); (c) an improved performance in Repeated Sprint Ability test. These findings suggest that a high-nitrate diet could be a feasible and effective strategy to improve exercise performance.

Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop.

In view of continuing unanswered questions regarding the geographical and demographic distribution of cardiovascular disease, and recent discoveries about the effects of dietary nitrate on cardiovascular physiology, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop to

High-nitrate vegetable diet increases plasma nitrate and nitrite concentrations and reduces blood pressure in healthy women.

Epidemiological studies suggest that green leafy vegetables, which are high in dietary nitrate, are protective against CVD such as stroke. High blood pressure (BP) is a major risk factor for stroke and inorganic nitrate has been shown to reduce BP. The objective of the present study was to test the hypothesis that diets containing high-nitrate (HN) vegetables would increase plasma nitrate and nitrite concentrations and reduce BP in healthy women. A randomized, crossover trial, where participants received HN vegetables (HN diet) or avoided HN vegetables (Control diet) for 1 week. Before and after each intervention, resting BP and plasma nitrate and nitrite concentrations were measured. University of Exeter, UK. Nineteen healthy women (mean age 20 (sd 2) years; mean BMI 22·5 (sd 3·8) kg/m2). The HN diet significantly increased plasma nitrate concentration (before HN diet: mean 24·4 (sd 5·6) µmol/l; after HN diet: mean 61·0 (sd 44·1) µmol/l, P<0·05) and plasma nitrite concentration (before HN diet: mean 98 (sd 91) nmol/l; after HN diet: mean 185 (sd 34) nmol/l, P<0·05). No significant change in plasma nitrate or nitrite concentration was observed after the Control diet. The HN diet significantly reduced resting systolic BP (before HN diet: mean 107 (sd 9) mmHg; after HN diet: mean 103 (sd 6) mmHg, P<0·05). No significant change in systolic BP was observed after the Control diet (before Control diet: mean 106 (sd 8) mmHg; after Control diet: mean 106 (sd 8) mmHg). Consumption of HN vegetables significantly increased plasma nitrate and nitrite concentrations and reduced BP in normotensive women.

Short-term effects of nitrate-rich green leafy vegetables on blood pressure and arterial stiffness in individuals with high-normal blood pressure

Evidence for a beneficial effect of dietary nitrate, through the nitrate–nitrite–NO pathway, on measures of cardiovascular function in healthy individuals is accumulating. It is less clear whether increased dietary nitrate intake from green leafy vegetables would have similar beneficial vascular effects in those at increased risk of developing hypertension. Our aim was to assess the effects of short-term regular consumption of increased nitrate from green leafy vegetables on blood pressure and arterial stiffness in individuals with high-normal blood pressure. Thirty-eight men and women ages 30–70 years with systolic blood pressure 120 to 139mm Hg were recruited to a randomized controlled crossover trial. The effects of a 7-day high-nitrate diet intervention (increased nitrate intake by at least 300mg/day from green leafy vegetables) were compared to a 7-day low-nitrate diet intervention. Outcome measures included pre- and postintervention salivary and plasma nitrate and nitrite concentrations; ambulatory, home, and office blood pressure; augmentation index; and carotid–femoral pulse wave velocity. The high-nitrate diet intervention resulted in at least a fourfold increase in salivary and plasma nitrate and nitrite (P<0.001). Ambulatory, home, and office blood pressure and arterial stiffness were not different between the high-nitrate diet and the low-nitrate diet. Increasing dietary nitrate intake in those with high-normal blood pressure and at increased risk of hypertension may not be an effective short-term strategy to lower blood pressure.

Dietary nitrate and reductive polyphenols may potentiate the vascular benefit and alleviate the ulcerative risk of low-dose aspirin

The recent revelation that daily low-dose aspirin not only lowers risk for vascular events, but also can notably decrease risk for a range of adenocarcinomas, decreasing total cancer mortality by about 20%, makes it highly desirable to implement this protective strategy on a population-wide basis. Nonetheless, the fact that low-dose aspirin approximately doubles risk for serious gastrointestinal bleeding may impede health authorities from recommending its use by people judged to be at low cardiovascular risk. Nitric oxide (NO) exerts gastroprotective effects by boosting blood flow and mucus production in the gastric mucosa – effects which demonstrably oppose the pro-ulcerative impact of aspirin and other NSAIDs. A nitrate-rich diet, as well as ingestion of reductive catechol-bearing polyphenols, can collaborate in promoting NO generation in gastric juice, and they are protective in rodent models of gastric ulceration. Moreover, a high-nitrate diet, as well as certain reductive polyphenols such as epicatechin and quercetin, can exert platelet-stabilizing effects complementary to those of aspirin, and act in other ways to preserve vascular health. Hence, diets rich in nitrate and reductive polyphenols have the potential to amplify the vascular-protective benefits of low-dose aspirin, while diminishing its pro-ulcerative risk. Low-dose aspirin may be more unequivocally recommendable within the context of such a dietary strategy.

Sugar highs and lows: the impact of diet on cognitive function.

In Western society, the prevalence of a hypercaloric diet consisting of a high sugar intake and highly processed foods coincided with an exponential rise in diabetes and metabolic syndrome as well as cardiovascular diseases and cancer. Evidence emphasizing the unfavourable effects of ‘irresponsible eating’ is emerging in regards to the big three Western diseases … cardiovascular disease, diabetes and cancer. Recent evidence has emerged supporting the connection between dietary intake and cognitive health, particularly in regards to the ageing population. A healthier diet during middle age years (B-vitamins, antioxidants, polyunsaturated fatty acids, etc.) was associated with better cognitive function later in life (Kesse-Guyot et al. 2012). In addition, higher polyphenol intake in the elderly was associated with better cognitive performance (Valls-Pedret et al. 2012). However, data on the effects of diet on learning, memory and cognition are scarce. Bowman et al. demonstrate a positive association between nutrient biomarker intake, cognitive function and brain volume (Bowman et al. 2012). Instead of providing additional data on a healthier diet and cognitive outcomes, the study by Agrawal and Gomez-Pinilla in a recent issue of The Journal of Physiology is one of the first to describe the negative consequence of a diet on learning and cognition (Agrawal & Gomez-Pinilla, 2012). The authors elegantly investigate the metabolic consequences of a high sugar intake coupled with a deficiency of omega-3 fatty acids on cognitive abilities and the potential association with insulin action and signalling mediators. As one might expect, the unhealthy diet (high fructose intake, low omega-3 fatty acids) was associated with lower cognitive scores and insulin resistance. In the vasculature, insulin is a vasodilator and increases blood flow to promote glucose delivery to the muscle and other tissue beds. This vasodilator function is blunted in insulin resistant individuals and suggests that an impairment of insulin action is coupled to a decreased perfusion of the tissues (Barrett et al. 2009). Obviously, chronic hypoperfusion to any tissue bed induces a multitude of problems (atrophy, etc.) and may further reduce insulin sensitivity. The same insulin/blood flow coupling mechanism may also be present in the cerebral circulation. Agrawal & Gomez-Pinilla demonstrate that animals with the highest insulin resistance index also have the longest latency time on a learning and memory challenge. Accordingly, we might expect that the animals with the highest insulin resistance may demonstrate a lower cerebral blood flow, and therefore less brain plasticity. In other words, insulin resistance and impairment of the insulin receptor signalling cascade in the hippocampus may be accompanied by decreasing regional blood flow and reduced memory. In humans, cerebral hypoperfusion is associated with lower cognitive function scores, and with dementia and lower brain volume (Rabbitt et al. 2006). Preventing or delaying the cognitive decline is of paramount importance with the expanding ageing population. The study by Agrawal & Gomez-Pinilla suggests that consuming omega-3 fatty acids and preventing insulin resistance may protect learning and memory ability with ageing. We might also suggest that maintaining optimum cerebral perfusion is also an important mechanism to preserve cognitive function. Along these lines, dietary interventions thought to improve peripheral perfusion or vascular function may also be operative in the brain. For example, the vasoprotective effects of a high nitrate diet shown in the periphery (Webb et al. 2008) and similar favourable changes in cerebral blood flow were recently reported after a high nitrate whole-food based dietary intervention (Presley et al. 2011). A similar case could be made for exercise interventions, which have parallel benefits on vascular function in the periphery and cerebral circulation, and are also associated with higher cognitive function scores. In summary, the study by Agrawal & Gomez-Pinilla provides mechanistic evidence linking poor dietary health and cognitive impairment. This observation is consistent with the idea that many important risk factors for cognitive decline with ageing have major effects on the vasculature. These risk factors include: diabetes, hypertension, hyperlipidaemia, sleep apnoea and physical inactivity. How these risk factors might interact with other pathophysiological mechanisms that contribute to cognitive decline is poorly understood, but the good news is that they are modifiable and that lifestyle-related public health guidelines are almost certainly protective against age-related cognitive decline.

Plasma nitrate and nitrite are increased by a high-nitrate supplement but not by high-nitrate foods in older adults

Little is known about the effect of dietary nitrate on the nitrate/nitrite/nitric oxide cycle in older adults. We examined the effect of a 3-day control diet vs high-nitrate diet, with and without a high-nitrate supplement (beetroot juice), on plasma nitrate and nitrite kinetics and blood pressure using a randomized 4-period crossover controlled design. We hypothesized that the high-nitrate diet would show higher levels of plasma nitrate/nitrite and lower blood pressure compared with the control diet, which would be potentiated by the supplement. Participants were 8 normotensive older men and women (5 female, 3 male, 72.5 ± 4.7 years old) with no overt disease or medications that affect nitric oxide metabolism. Plasma nitrate and nitrite levels and blood pressure were measured before and hourly for 3 hours after each meal. The mean daily changes in plasma nitrate and nitrite were significantly different from baseline for both control diet + supplement (P < .001 and P = .017 for nitrate and nitrite, respectively) and high-nitrate diet + supplement (P = .001 and P = .002), but not for control diet (P = .713 and P = .741) or high-nitrate diet (P = .852 and P = .500). Blood pressure decreased from the morning baseline measure to the three 2-hour postmeal follow-up time points for all treatments, but there was no main effect for treatment. In healthy older adults, a high-nitrate supplement consumed at breakfast elevated plasma nitrate and nitrite levels throughout the day. This observation may have practical utility for the timing of intake of a nitrate supplement with physical activity for older adults with vascular dysfunction.

P32. Acute effect of a high nitrate diet on brain perfusion in older adults

P32. Acute effect of a high nitrate diet on brain perfusion in older adults

Acute effect of a high nitrate diet on brain perfusion in older adults

AimsPoor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and resultsIn this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. ConclusionThese results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

Acute Effect of a High Nitrate Diet on Brain Perfusion in Older Adults

Acute Effect of a High Nitrate Diet on Brain Perfusion in Older Adults

PH-dependent nitration of para-hydroxyphenylacetic acid in the stomach

The major urinary metabolite of nitrotyrosine is 3-nitro-4-hydroxyphenylacetic acid (3-Nitro-HPA). However, recent animal studies have shown that the majority of urinary 3-Nitro-HPA is derived from nitration of endogenous para-hydroxyphenylacetic acid (HPA), a metabolite of tyrosine. One potential site for the formation of 3-Nitro-HPA is the stomach, where nitrous acid is formed by the reaction of nitrite in saliva with gastric acid. The aim of this study was to determine whether there is pH-dependent nitration of salivary para-hydroxyphenylacetic acid or tyrosine, and the effects of dietary nitrate. Healthy volunteers ( n = 18) ingested either a low or high nitrate diet, with and without the administration of omeprazole, a proton pump inhibitor. Urinary 3-Nitro-HPA excretion increased from 197 ± 52 to 319 ± 88 μg/day on switching from a low to a high nitrate diet ( P < 0.05), and decreased (166 ± 53 μg/day, P < 0.05) when gastric pH was increased by omeprazole. To determine whether 3-Nitro-HPA can be formed by nitration of para-hydroxyphenylacetic acid in the stomach, 500 μg of deuterated para-hydroxyphenylacetic acid was ingested with a high nitrate meal. This led to the excretion of both deuterated HPA and 3-Nitro-HPA in the urine, confirming that para-hydroxyphenylacetic acid is absorbed, and nitrated. Since omeprazole decreases the formation of 3-Nitro-HPA, presumably by decreasing the nitration of endogenous para-hydroxyphenylacetic acid present in saliva, and the observation that ingested deuterated para-hydroxyphenylacetic acid is nitrated and excreted, we conclude that endogenous para-hydroxyphenylacetic acid is nitrated in the stomach, absorbed, and excreted as 3-Nitro-HPA.

Effects of pH and Electron Donors on Nitrate and Nitrite Reduction in Ruminal Microbiota

Factors affecting nitrate and nitrite reduction in the rumen were examined. Nitrate and nitrite reduction by mixed microbes harvested from the goat rumen was increased by feeding a high-roughage diet, which contained a much higher amount of nitrate than concentrate. The activities of nitrate reductase and nitrite reductase per bacterial mass appeared to be increased by feeding a high-nitrate diet, suggesting that these enzymes are induced by substrates. Nitrate and nitrite reduction was confirmed to be the fastest at neutral pH and affected by electron supply. The supplementation of electron donors, such as formate, H2, and lactate, stimulated nitrate and nitrite reduction, especially nitrite reduction, which decreased nitrite accumulation. As a result, addition of formate or lactate in the presence of nitrate alleviated the inhibitory effect of nitrite on fermentation, and greatly reduced methanogenesis.

Urine samples before dinner are preferable when studying changes in endogenous nitrate production under uncontrolled dietary conditions

Changes in nitric oxide production result in changes in nitrate excretion, but these are difficult to detect if the daily intake of nitrate varies substantially. Instead of using a sample of the combined urine produced in 24 h for analysis, we studied the urine nitrate concentration in urine discharge at various times of the day. This was done with urine samples from each of seven men after a high dietary nitrate intake, followed by a low dietary intake 24 h later. The lowest variability in nitrate concentration was found in the samples before dinner (late afternoon) (511 ± 201 (S.D.) μmol/1). However, the pre-dinner samples after a day with a nitrate-rich meal had still a 40% increased nitrate concentration (623 ± 147 μmol/1), when compared with samples before the high nitrate diet (440 ± 90 μmol/1; P < 0.05). This effect disappeared on the second day after the high nitrate meal (476 ± 108 μmol/1). Similar results were found when using the nitrate/creatinine ratio. We conclude that urine samples taken before nitrate rich meals are the most reliable samples for estimating (changes in) endogenous nitrate production.