Is vitamin C a booster of the effects of dietary nitrate on endothelial function? Physiologic rationale and implications for research.

Endothelial dysfunction (ED) is an early marker of vascular damage linked to the loss of integrity of the endothelial lining and represents a key step in the pathogenesis of atherosclerosis and cardiovascular diseases (CVDs). ED may be reversible, hence the development and testing of effective early interventions could be beneficial for the prevention and treatment of CVDs. Recent studies have demonstrated that the consumption of dietary nitrate (NO3-), an inorganic anion that serves as a substrate for the gas transmitter nitric oxide (NO), can lower blood pressure, improve endothelial function and, in observational studies, reduce the risk for CVD. We hypothesize that the co-consumption of NO3- with vitamin C, which is a potent antioxidant, could enhance the "yield" of NO produced from a given NO3- dose byThis could translate into greater NO-dependent effects on endothelial function (EF) and overall vascular health (than may be experienced with NO3- supplementation alone). This review presents evidence to suggest that the combination of vitamin C and dietary nitrate could represent a promising and effective approach to improve EF and reduce CVD risk, and discuss opportunities for future research.

Moderate doses of dietary nitrate elicit greater effects on blood pressure and endothelial function than a high dose: A 13-week pilot study.

BACKGROUND & AIMS: Few studies have explored the prolonged effects of dietary nitrate on vascular health. This pilot study tested the effects of prolonged consumption (13 weeks) of a range of doses of dietary nitrate (NO3-), provided as beetroot juice (BJ), on blood pressure (BP) and endothelial function in overweight and obese older participants. METHODS AND RESULTS: Sixty-two overweight or obese older participants (60-75 years) were randomized to the following interventions: (1) high NO3- (2) medium NO3-, (3) low NO3-, or (4) placebo. Resting clinic and home BP were measured pre- and post-intervention. Laser Doppler iontophoresis was used to quantify changes in endothelial-dependent and independent microvascular blood flow. RESULTS: This pilot study showed that medium and low doses of NO3- were more effective in lowering resting-clinic SBP (P = 0.04 and, P = 0.03, respectively) than was PL. The lower doses of NO3- also resulted in significant increases in microvascular perfusion (medium, P = 0.02; low, P = 0.002) relative to baseline values. CONCLUSION: These findings indicate that supplementation with medium and low, but not high, doses of NO3- for 13 weeks had positive effects on BP and endothelial function in older overweight and obese adults. These findings require confirmation in larger studies.

Caloric Restriction (CR) Plus High-Nitrate Beetroot Juice Does Not Amplify CR-Induced Metabolic Adaptation and Improves Vascular and Cognitive Functions in Overweight Adults: A 14-Day Pilot Randomised Trial.

Caloric restriction (CR) and dietary nitrate supplementation are nutritional interventions with pleiotropic physiological functions. This pilot study investigates the combined effects of CR and nitrate-rich beetroot juice (BRJ) on metabolic, vascular, and cognitive functions in overweight and obese middle-aged and older adults. This was a two-arm, parallel randomized clinical trial including 29 participants allocated to CR + BRJ (n = 15) or CR alone (n = 14) for 14 days. Body composition, resting energy expenditure (REE), and hand-grip strength were measured. Resting blood pressure (BP) and microvascular endothelial function were measured, and Trail-Making Test A and B were used to assess cognitive function. Salivary nitrate and nitrite, and urinary nitrate and 8-isoprostane concentrations were measured. Changes in body composition, REE, and systolic and diastolic BP were similar between the two interventions (p > 0.05). The CR + BRJ intervention produced greater changes in average microvascular flux (p = 0.03), NO-dependent endothelial activity (p = 0.02), and TMT-B cognitive scores (p = 0.012) compared to CR alone. Changes in urinary 8-isoprostane were greater in the CR + BRJ group (p = 0.02), and they were inversely associated with changes in average microvascular flux (r = -0.53, p = 0.003). These preliminary findings suggest that greater effects on vascular and cognitive functions could be achieved by combining CR with dietary nitrate supplementation.

Dietary nitrate, aging and brain health: the latest evidence.

PURPOSE OF REVIEW: With an increasing population age, cognitive decline and age-associated neurodegenerative diseases are becoming increasingly prevalent and burdensome in society. Dietary supplementation with inorganic nitrate, which serves as a nitric oxide precursor, has been suggested as a potential nutritional strategy to improve brain health in older adults. In this review, we discuss recent findings in this area. RECENT FINDINGS: A number of studies have emerged in the past 12-18 months exploring the effects of dietary nitrate supplementation on cognitive function, with typically (although not exclusively) null findings emerging. This research is characterized by small, acute/short-term studies, although observational studies and longer-duration randomised controlled trials are beginning to emerge. From the limited research reporting benefits of nitrate supplementation on cognitive function, one important discovery has been the identification of a potential pathway through which nitrate could impact cognitive health, involving modulation of the oral microbiome, which warrants further investigation. SUMMARY: Despite some promising early findings, there is currently insufficient evidence to recommend increased dietary nitrate intake for the purpose of improving brain health. However, longer-term, larger-scale trials in potentially responsive groups are warranted to provide definitive evidence in this area.

Nitric oxide, aging and aerobic exercise: Sedentary individuals to Master's athletes.

Aging is associated with a decline in physiological function and exercise performance. These effects are mediated, at least in part, by an age-related decrease in the bioavailability of nitric oxide (NO), a ubiquitous gasotransmitter and regulator of myriad physiological processes. The decrease in NO bioavailability with aging is especially apparent in sedentary individuals, whereas older, physically active individuals maintain higher levels of NO with advancing age. Strategies which enhance NO bioavailability (including nutritional supplementation) have been proposed as a potential means of reducing the age-related decrease in physiological function and enhancing exercise performance and may be of interest to a range of older individuals including those taking part in competitive sport. In this brief review we discuss the effects of aging on physiological function and endurance exercise performance, and the potential role of changes in NO bioavailability in these processes. We also provide a summary of current evidence for dietary supplementation with substrates for NO production - including inorganic nitrate and nitrite, l-arginine and l-citrulline - for improving exercise capacity/performance in older adults. Additionally, we discuss the (limited) evidence on the effects of (poly)phenols and other dietary antioxidants on NO bioavailability in older individuals. Finally, we provide suggestions for future research.

Dietary Inorganic Nitrate as an Ergogenic Aid: An Expert Consensus Derived via the Modified Delphi Technique.

INTRODUCTION: Dietary inorganic nitrate is a popular nutritional supplement, which increases nitric oxide bioavailability and may improve exercise performance. Despite over a decade of research into the effects of dietary nitrate supplementation during exercise there is currently no expert consensus on how, when and for whom this compound could be recommended as an ergogenic aid. Moreover, there is no consensus on the safe administration of dietary nitrate as an ergogenic aid. This study aimed to address these research gaps. METHODS: The modified Delphi technique was used to establish the views of 12 expert panel members on the use of dietary nitrate as an ergogenic aid. Over three iterative rounds (two via questionnaire and one via videoconferencing), the expert panel members voted on 222 statements relating to dietary nitrate as an ergogenic aid. Consensus was reached when > 80% of the panel provided the same answer (i.e. yes or no). Statements for which > 80% of the panel cast a vote of insufficient evidence were categorised as such and removed from further voting. These statements were subsequently used to identify directions for future research. RESULTS: The 12 panel members contributed to voting in all three rounds. A total of 39 statements (17.6%) reached consensus across the three rounds (20 yes, 19 no). In round one, 21 statements reached consensus (11 yes, 10 no). In round two, seven further statements reached consensus (4 yes, 3 no). In round three, an additional 11 statements reached consensus (5 yes, 6 no). The panel agreed that there was insufficient evidence for 134 (60.4%) of the statements, and were unable to agree on the outcome of the remaining statements. CONCLUSIONS: This study provides information on the current expert consensus on dietary nitrate, which may be of value to athletes, coaches, practitioners and researchers. The effects of dietary nitrate appear to be diminished in individuals with a higher aerobic fitness (peak oxygen consumption [V̇O2peak] > 60 ml/kg/min), and therefore, aerobic fitness should be taken into account when considering use of dietary nitrate as an ergogenic aid. It is recommended that athletes looking to benefit from dietary nitrate supplementation should consume 8-16 mmol nitrate acutely or 4-16 mmol/day nitrate chronically (with the final dose ingested 2-4 h pre-exercise) to maximise ergogenic effects, taking into consideration that, from a safety perspective, athletes may be best advised to increase their intake of nitrate via vegetables and vegetable juices. Acute nitrate supplementation up to ~ 16 mmol is believed to be safe, although the safety of chronic nitrate supplementation requires further investigation. The expert panel agreed that there was insufficient evidence for most of the appraised statements, highlighting the need for future research in this area.

Incremental Doses of Nitrate-Rich Beetroot Juice Do Not Modify Cognitive Function and Cerebral Blood Flow in Overweight and Obese Older Adults: A 13-Week Pilot Randomised Clinical Trial.

Nitrate-rich food increases nitric oxide (NO) production and may have beneficial effects on vascular, metabolic, and brain function. This pilot study tested the effects of prolonged consumption of a range of doses of dietary nitrate (NO3-), provided as beetroot juice, on cognitive function and cerebral blood flow (CBF) in overweight and obese older participants. The study had a 13-week single-blind, randomised, parallel design, and 62 overweight and obese older participants (aged 60 to 75 years) received the following interventions: (1) high NO3- (2 × 70 mL beetroot juice/day) (2) medium NO3- (70 mL beetroot juice/day), (3) low NO3- (70 mL beetroot juice on alternate days), or (4) placebo (70 mL of NO3--depleted beetroot juice on alternate days). Cognitive functions were assessed using the Computerised Mental Performance Assessment System (COMPASS) assessment battery. CBF, monitored by concentration changes in oxygenated and deoxygenated haemoglobin, was assessed in the frontal cortex using near-infrared spectroscopy. The findings of this pilot study showed that cognitive function and CBF were not affected by supplementation with NO3--rich beetroot juice for 13 weeks, irrespective of the NO3- dose administered. These findings require confirmation in larger studies using more sophisticated imaging methods (i.e., MRI) to determine whether prolonged dietary NO3- supplementation influences brain function in older overweight people.

The Effect of Nitrate-Rich Beetroot Juice on Markers of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Human Intervention Trials.

This systematic review and meta-analysis of randomized controlled trials examined whether dietary nitrate supplementation attenuates exercise-induced muscle damage (EIMD) and is reported according to the PRISMA guidelines. Medline and SPORTDiscus databases were searched from inception to June 2020. Inclusion criteria were studies in adult humans consuming inorganic nitrate before and after exercise and that measured markers implicated in the etiology of EIMD (muscle function, muscle soreness, inflammation, myocellular protein efflux, oxidative stress, range of motion) <168 h post. The Cochrane Collaboration risk of bias two tool was used to critically appraise the studies; forest plots were generated with random-effects models and standardized mean differences (SMD). Nine studies were included in the systematic review and six in the meta-analysis. All studies were rated to have some concerns for risk of bias. All trials in the meta-analysis provided nitrate as beetroot juice, which accelerated isometric strength recovery 72 h post-exercise (SMD: 0.54, p = 0.01) and countermovement jump performance 24-72 h post-exercise (SMD range: 0.75-1.32, p < 0.03). Pressure pain threshold was greater with beetroot juice 48 (SMD: 0.58, p = 0.03) and 72 h post-exercise (SMD: 0.61, p = 0.02). Beetroot juice had no effect on markers of oxidative stress and creatine kinase (p > 0.05), but c-reactive protein was higher vs. placebo at 48 h post-exercise (SMD: 0.55, p = 0.03). These findings suggest that nitrate-rich beetroot juice may attenuate some markers of EIMD, but more large-scale controlled trials in elite athletes are needed.

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults.

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO3-) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m2) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO3- (HN: 2 × 70 mL BJ/day) (2) medium-NO3- (MN: 70 mL BJ/day), (3) low-NO3- (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO3--depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO3- intake, and by measuring NO3- and NO2- concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO3- dose and the increase in plasma and urinary NO3- concentration (R2 = 0.71, P < 0.001 and R2 = 0.46 P < 0.001, respectively), but relationships between NO3- dose and changes in salivary NO3- and NO2- were non-linear (R2 = 0.35, P = 0.002 and R2 = 0.23, P = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.

Feasibility and acceptability of a nutritional intervention testing the effects of nitrate-rich beetroot juice and folic acid on blood pressure in Tanzanian adults with elevated blood pressure.

Sub-Saharan African countries are experiencing an alarming increase in hypertension prevalence. This study evaluated the feasibility and acceptability of nitrate-rich beetroot and folate supplementation, alone or combined, for the reduction of blood pressure (BP) in Tanzanian adults with elevated BP. This was a three-arm double-blind, placebo-controlled, parallel randomised clinical trial. Forty-eight participants were randomised to one of three groups to follow a specific 60-day intervention which included a: (1) combined intervention (beetroot juice + folate), (2) single intervention (beetroot juice + placebo), and (3) control group (nitrate-depleted beetroot juice + placebo). Forty-seven participants (age: 50-70 years) completed the study. The acceptability of the interventions was high. Self-reported compliance to the interventions was more than 90% which was confirmed by the significant increase in nitrate and folate concentrations in plasma and saliva samples in the treatment arms. This study provides important information for the design of high-nitrate interventions to reduce BP in Sub-Saharan African countries.

Nitrate-Rich Beetroot Juice Reduces Blood Pressure in Tanzanian Adults with Elevated Blood Pressure: A Double-Blind Randomized Controlled Feasibility Trial.

BACKGROUND: In Sub-Saharan Africa, current strategies are struggling to control the burgeoning hypertension epidemic. Dietary interventions such as inorganic nitrate or folic acid supplementation could represent promising strategies for reducing blood pressure (BP) in this setting. OBJECTIVES: This feasibility study explores the effects of dietary inorganic nitrate supplementation, alone or in combination with folic acid, on BP in Tanzanian adults with elevated BP in Tanzania. METHODS: A placebo-controlled, double-blind, randomized controlled feasibility trial was conducted. Forty-seven middle-aged and older participants (age: 50-70 y, BMI: 26.3-29.1 kg/m2) were randomly assigned to 3 conditions for a period of 60 d: 1) high-nitrate beetroot juice (∼400 mg nitrate) and folic acid (∼5 mg folic acid) (N + F), 2) high-nitrate beetroot juice and placebo (N + P), or 3) nitrate-depleted beetroot juice and placebo (P + P). Clinic and 24-h ambulatory BP and measurements of compliance in plasma (nitrate and folate concentrations) and saliva (nitrate and nitrite) were obtained at baseline, 30 d, and 60 d. RESULTS: Baseline resting systolic and diastolic BP (mean ± SD) was 151.0 ± 19.4 mm Hg and 91.8 ± 11.7 mm Hg, respectively. Compliance to the interventions was high (>90%) in all groups which was confirmed by the significant increase in nitrate and folic acid concentrations in plasma and saliva samples in the treatment arms. After 60 d, 24-h systolic BP dropped by -10.8 ± 9.8 mm Hg (P < 0.001), -6.1 ± 13.2 mm Hg (P = 0.03), and -0.3 ± 9.7 mm Hg (P = 0.83) in the N + P, N + F, and P + P groups, respectively. There was a significant decrease in 24-h diastolic BP in the N + P group (-5.4 ± 5.0 mm Hg, P = 0.004), whereas changes were not significant in the N + F (-1.8 ± 8.1 mm Hg, P = 0.32) and P + P (1.6 ± 8.3 mm Hg, P = 0.43) groups. CONCLUSIONS: Dietary inorganic nitrate represents a potential nutritional strategy to lessen the hypertension epidemic in Sub-Saharan Africa. These findings support the rationale for future long-term investigations exploring the efficacy of dietary nitrate for lowering BP and attenuating cardiovascular disease risk in this setting.This trial was registered at isrctn.com as ISRCTN67978523.

It's No Has Bean: A Review of the Effects of White Kidney Bean Extract on Body Composition and Metabolic Health.

The rising prevalence of overweight and obesity is a global concern, increasing the risk of numerous non-communicable diseases and reducing quality of life. A healthy diet and exercise remain the cornerstone treatments for obesity. However, adherence rates can be low and the effectiveness of these interventions is often less than anticipated, due to compensatory changes in other aspects of the energy balance equation. Whilst some alternative weight-loss therapies are available, these strategies are often associated with side effects and are expensive. An alternative or adjunct to traditional weight-loss approaches may be the use of bioactive compounds extracted from food sources, which can be incorporated into habitual diet with a low cost and minimal burden. One product which has attracted attention in this regard is white kidney bean extract (WKBE), which has been suggested to inhibit the enzyme α-amylase, limiting carbohydrate digestion and absorption with small but potentially meaningful attendant beneficial effects on body weight and metabolic health. In this review, drawing evidence from both human and animal studies, we discuss the current evidence around the effects of WKBE on body composition and metabolic health. In addition, we discuss evidence on the safety of this supplement and explore potential directions for future research.

Effects of inorganic nitrate and vitamin C co-supplementation on blood pressure and vascular function in younger and older healthy adults: A randomised double-blind crossover trial.

BACKGROUND: Vitamin C and inorganic nitrate have been linked to enhanced nitric oxide (NO) production and reduced oxidative stress. Vitamin C may also enhance the conversion of nitrite into NO. AIMS: We investigated the potential acute effects of vitamin C and inorganic nitrate co-supplementation on blood pressure (BP) and peripheral vascular function. The secondary aim was to investigate whether age modified the effects of vitamin C and inorganic nitrate on these vascular outcomes. METHODS: Ten younger (age 18-40 y) and ten older (age 55-70 y) healthy participants were enrolled in a randomised double-blind crossover clinical trial. Participants ingested a solution of potassium nitrate (7 mg/kg body weight) and/or vitamin C (20 mg/kg body weight) or their placebos. Acute changes in resting BP and vascular function (post-occlusion reactive hyperemia [PORH], peripheral pulse wave velocity [PWV]) were monitored over a 3-h period. RESULTS: Vitamin C supplementation reduced PWV significantly (vitamin C: -0.70 ± 0.31 m/s; vitamin C placebo: +0.43 ± 0.30 m/s; P = 0.007). There were significant interactions between age and vitamin C for systolic, diastolic, and mean arterial BP (P = 0.02, P = 0.03, P = 0.02, respectively), with systolic, diastolic and mean BP decreasing in older participants and diastolic BP increasing in younger participants following vitamin C administration. Nitrate supplementation did not influence BP (systolic: P = 0.81; diastolic: P = 0.24; mean BP: P = 0.87) or vascular function (PORH: P = 0.05; PWV: P = 0.44) significantly in both younger and older participants. However, combined supplementation with nitrate and vitamin C reduced mean arterial BP (-2.6 mmHg, P = 0.03) and decreased PWV in older participants (PWV: -2.0 m/s, P = 0.02). CONCLUSIONS: The co-administration of a single dose of inorganic nitrate and vitamin C lowered diastolic BP and improved PVW in older participants. Vitamin C supplementation improved PWV in both age groups but decreased systolic and mean BP in older participants only. CLINICAL TRIAL REGISTRATION: Current Controlled Trials (ISRCTN98942199).

Appetite and energy intake responses to breakfast consumption and carbohydrate supplementation in hypoxia.

PURPOSE: The purpose of experiment one was to determine the appetite, acylated ghrelin and energy intake response to breakfast consumption and omission in hypoxia and normoxia. Experiment two aimed to determine the appetite, acylated ghrelin and energy intake response to carbohydrate supplementation after both breakfast consumption and omission in hypoxia. METHODS: In experiment one, twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. In experiment two, eleven participants rested and exercised in normobaric hypoxia (4300 m: FiO2 ~11.7%), twice after consuming a high carbohydrate breakfast and twice after breakfast omission. Participants consumed both a carbohydrate (1.2g·min-1 glucose) and a placebo beverage after breakfast consumption and omission. Measures of appetite perceptions and acylated ghrelin were taken at regular intervals throughout both experiments and an ad-libitum meal was provided post-exercise to quantify energy intake. RESULTS: Breakfast consumption had no significant effect on post exercise energy intake or acylated ghrelin concentrations, despite reductions in appetite perceptions. As such, breakfast consumption increased total trial energy intake compared with breakfast omission in hypoxia (7136 ± 2047 kJ vs. 5412 ± 1652 kJ; p = 0.02) and normoxia (9276 ± 3058 vs. 6654 ± 2091 kJ; p < 0.01). Carbohydrate supplementation had no effect on appetite perceptions or acylated ghrelin concentrations after breakfast consumption or omission. As such, carbohydrate supplementation increased total energy intake after breakfast consumption (10222 ± 2831 kJ vs. 7695 ± 1970 kJ p < 0.01) and omission (8058 ± 2574 kJ vs. 6174 ± 2222 kJ p = 0.02). CONCLUSION: Both breakfast consumption and carbohydrate supplementation provide beneficial dietary interventions for increasing energy intake in hypoxic conditions.

Validity and reliability of test strips for the measurement of salivary nitrite concentration with and without the use of mouthwash in healthy adults.

The nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway has received considerable interest in recent years as a potential target for nutritional interventions designed to increase NO production, and elicit therapeutic effects in humans. In particular, studies have evaluated the effects of supplemental dietary NO3-, which serves as a 'substrate' for this pathway, on numerous different health outcomes. One challenge has been to evaluate compliance with the NO3- interventions. A recent advance in this field has been the development of a non-invasive, simple and rapid method to measure nitrite concentrations in saliva using small test salivary strips. In the present study, ten healthy adults were recruited to a randomised, crossover study and received an acute dose of NO3--rich beetroot juice (BJ) after rinsing their mouth with either water or commercially available antibacterial mouthwash. Salivary NO3- and NO2- concentrations were measured at baseline and up to 5 h after BJ consumption using the gold-standard chemiluminescence and a colorimetric Griess assay. In addition, two salivary test strips (Berkeley Test strips, CA, USA) were used to measure NO2-concentrations at the same time points. Five observers read the strips and inter- and intra-observer reliability was measured. The Bland-Altman method was used to provide a visual representation of the agreement between the methods used to evaluate salivary NO3-/NO2-concentration. Sialin concentrations were measured at baseline and up to 5 h after BJ consumption. BJ elevated salivary NO3- and NO2- concentrations when the mouth was rinsed with water (both P < 0.01), as assessed via both chemiluminescence and Griess methods. Rinsing the mouth with antibacterial mouthwash attenuated markedly the increase in NO2- (P < 0.001), while NO3-concentrations were unaffected (P > 0.05). The Intra-Class Coefficients of Correlation (ICC) showed a high inter- and intra-observer reliability (r > 0.8). A significant positive correlation was found between absolute salivary NO2- concentrations measured by strips and Griess and chemiluminescence methods (rho = 0.83 and 0.77, respectively) and also when expressed as changes in salivary NO2- concentrations (rho = 0.80 and 0.79, respectively). Bland Altman analysis indicated a poor agreement for absolute NO2- concentrations between salivary strips and the chemiluminescence and Griess methods. A small significant negative correlation was found between changes in salivary sialin and salivary NO2- concentrations (r = -0.20, P = 0.04). A non-significant positive correlation was observed between the change in salivary sialin and salivary NO3- concentrations (r = 0.18, P = 0.06). This study suggests that commercially available salivary NO2- test strips provide a reasonable surrogate marker for monitoring changes in salivary NO2- concentrations in humans. However, the strips do not provide accurate estimates of absolute NO2- concentrations.

Effects of inorganic nitrate and nitrite consumption on cognitive function and cerebral blood flow: A systematic review and meta-analysis of randomized clinical trials.

We conducted a systematic review and meta-analysis of randomized clinical trials examining the effect of inorganic nitrate or nitrite supplementation on cognitive function (CF) and cerebral blood flow (CBF). Two databases (PubMed, Embase) were searched for articles from inception until May 2017. Inclusion criteria were: randomized clinical trials; participants >18 years old; trials comparing a nitrate/nitrite intervention with a control. Thirteen and nine trials were included in the meta-analysis to assess CF and CBF, respectively. Random-effects models were used and the effect size described as standardized mean differences (SMDs). A total of 297 participants (median of 23 per trial) were included for CF; 163 participants (median of 16 per trial) were included for CBF. Nitrate/nitrite supplementation did not influence CF (SMD +0.06, 95% CI: -0.06, 0.18, P = 0.32) or CBF under resting (SMD +0.14, 95% CI: -0.13, 0.41, P = 0.31), or stimulated conditions (SMD + 0.23, 95% CI: -0.11, 0.56, P = 0.19). The meta-regression showed an inverse association between duration of the intervention and CBF (P = 0.02) but no influence of age, BMI or dose (P < 0.05). Nitrate and nitrite supplementation did not modify CBF or CF. Further trials employing larger samples sizes and interventions with longer duration are warranted.

Does dietary nitrate say NO to cardiovascular ageing? Current evidence and implications for research.

CVD are characterised by a multi-factorial pathogenesis. Key pathogenetic steps in the development of CVD are the occurrence of endothelial dysfunction and formation of atherosclerotic lesions. Reduced nitric oxide (NO) bioavailability is a primary event in the initiation of the atherosclerotic cascade. NO is a free radical with multiple physiological functions including the regulation of vascular resistance, coagulation, immunity and oxidative metabolism. The synthesis of NO proceeds via two distinct pathways identified as enzymatic and non-enzymatic. The former involves the conversion of arginine into NO by the NO synthases, whilst the latter comprises a two-step reducing process converting inorganic nitrate into nitrite and subsequently NO.Inorganic is present in water and food, particularly beetroot and green leafy vegetables. Several investigations have therefore used the non-enzymatic NO pathway as a target for nutritional supplementation ( salts) or dietary interventions (high- foods) to increase NO bioavailability and impact on cardiovascular outcomes. Some studies have reported positive effects of dietary on systolic blood pressure and endothelial function in patients with hypertension and chronic heart failure. Nevertheless, results have been inconsistent and the size of the effect appears to be declining in older individuals. Additionally, there is a paucity of studies for disorders such as diabetes, CHD and chronic kidney failure. Thus, whilst dietary supplementation could represent an effective and viable strategy for the primary and secondary prevention of age-related cardiovascular and metabolic diseases, more large-scale, robust studies are awaited to confirm or refute this notion.

The Effect of a Dietary Nitrate Supplementation in the Form of a Single Shot of Beetroot Juice on Static and Dynamic Apnea Performance.

INTRODUCTION: The purpose of the present study was to assess the effects of acute nitrate ([Formula: see text])-rich beetroot juice (BRJ) supplementation on peripheral oxygen saturation (SpO2), heart rate (HR), and pulmonary gas exchange during submaximal static and dynamic apnea. METHODS: Nine (six males and three females) trained apneists (age: 39.6 ± 8.2 years, stature: 170.4 ± 11.5 cm, and body mass: 72.0 ± 11.5 kg) performed three submaximal static apneas at 60%, 70%, and 80% of the participant's current reported personal best time, followed by three submaximal (∼75% or personal best distance) dynamic apneas following the consumption of either a 70-ml concentrated BRJ (7.7 mmol [Formula: see text]) or a [Formula: see text]-depleted placebo (PLA; 0.1 mmol [Formula: see text]) in double-blind randomized manner. HR and SpO2 were measured via fingertip pulse oximetry at the nadir, and online gas analysis was used to assess pulmonary oxygen uptake ([Formula: see text]) during recovery following breath-holds. RESULTS: There were no differences (p < .05) among conditions for HR (PLA = 59 ± 11 bpm and BRJ = 61 ± 12 bpm), SpO2 (PLA = 83% ± 14% and BRJ = 84% ±9%), or [Formula: see text] (PLA = 1.00 ± 0.22 L/min and BRJ = 0.97 ± 0.27 L/min). CONCLUSION: The consumption of 7.7 mmol of beetroot juice supplementation prior to a series of submaximal static and dynamic apneas did not induce a significant change in SpO2, HR, and [Formula: see text] when compared with placebo. Therefore, there is no apparent physiological response that may benefit free divers as a result of the supplementation.

Physiological and performance effects of nitrate supplementation during roller-skiing in normoxia and normobaric hypoxia.

The present study examined the effects of acute nitrate (NO3-) supplementation ingested in the form of concentrated beetroot juice on cross-country roller-ski performance in normoxia (N) and normobaric hypoxia (H). Eight competitive cross-country skiers (five males: age 22 ± 3 years, V·O2max 71.5 ± 4.7 mL kg-1·min-1; three females: age 21 ± 1 years, V·O2max 58.4 ± 2.5 mL kg-1·min-1) were supplemented with a single dose of NO3--rich beetroot juice (BRJ, ∼13 mmol NO3-) or a NO3--depleted placebo (PL, ∼0 mmol NO3-) and performed 2 x 6-min submaximal exercise bouts and a 1000-m time-trial (TT) on a treadmill in N (20.9% O2) or H (16.8% O2). The four experimental trials were presented in a randomised, counter-balanced order. Plasma NO3- and nitrite concentrations were significantly higher following BRJ compared to PL (both p < 0.001). However, respiratory variables, heart rate, blood lactate concentration, ratings of perceived exertion, and near-infrared spectroscopy-derived measures of muscle tissue oxygenation during submaximal exercise were not significantly different between BRJ and PL (all p > 0.05). Likewise, time to complete the TT was unaffected by supplementation in both N and H (p > 0.05). In conclusion, an acute dose of ∼13 mmol NO3- does not affect physiological or performance responses to submaximal or maximal treadmill roller-skiing in competitive cross-country skiers exercising in N and H.

"Beet-ing" the Mountain: A Review of the Physiological and Performance Effects of Dietary Nitrate Supplementation at Simulated and Terrestrial Altitude.

Exposure to altitude results in multiple physiological consequences. These include, but are not limited to, a reduced maximal oxygen consumption, drop in arterial oxygen saturation, and increase in muscle metabolic perturbations at a fixed sub-maximal work rate. Exercise capacity during fixed work rate or incremental exercise and time-trial performance are also impaired at altitude relative to sea level. Recently, dietary nitrate (NO3-) supplementation has attracted considerable interest as a nutritional aid during altitude exposure. In this review, we summarise and critically evaluate the physiological and performance effects of dietary NO3- supplementation during exposure to simulated and terrestrial altitude. Previous investigations at simulated altitude indicate that NO3- supplementation may reduce the oxygen cost of exercise, elevate arterial and tissue oxygen saturation, improve muscle metabolic function, and enhance exercise capacity/performance. Conversely, current evidence suggests that NO3- supplementation does not augment the training response at simulated altitude. Few studies have evaluated the effects of NO3- at terrestrial altitude. Current evidence indicates potential improvements in endothelial function at terrestrial altitude following NO3- supplementation. No effects of NO3- supplementation have been observed on oxygen consumption or arterial oxygen saturation at terrestrial altitude, although further research is warranted. Limitations of the present body of literature are discussed, and directions for future research are provided.