Carrot intake is consistently negatively associated with cancer incidence: A systematic review and meta-analysis of prospective observational studies.

Carrots are main dietary sources of several potential anti-cancer compounds, including polyacetylenes, while ß-carotene has shown no benefits in controlled cancer trials. Accordingly, associations between carrot intake and cancer incidence were quantified, where necessary using α-carotene as a non-causal biomarker of carrot consumption, by searching for studies published before June 2022 reporting risk estimates for relationships of cancer incidence with carrot intake or α-carotene intake or α-carotene plasma concentration, supplemented with hand searches of included studies and reviews. Meta-analyses comparing highest and lowest reported intakes in prospective studies using a random-effects model estimated summary relative risks (RRs) with 95% confidence intervals (CIs), separately for carrot intake or α-carotene plasma concentration, and the corresponding dose-responses. Of 198 observational studies, in 50 prospective studies with 52000 cases recording carrot intake, the cancer-risk was substantially reduced (RR 0.90, 95% CI 0.87-0.94, p ˂ 0·00004). In 30 prospective studies with 9331 cases reporting plasma α-carotene levels, summary RR was 0.80 (0.72-0.89, p ˂ 0·00006). For both exposure types, inter-study heterogeneity was moderate, interaction with cancer types insignificant, and the dose-response significant (p ˂ 0·01). In conclusion, carrot consumption is robustly associated with decreased cancer-risk; carrot consumption should be encouraged, and the causal mechanisms further investigated.

Effects of dietary nitrate and vitamin C co-ingestion on blood pressure and hand-grip strength in young adults.

Background: Co-administration of vitamin C and inorganic nitrate ([Formula: see text]) may reduce oxidative stress, boost the conversion of nitrite ([Formula: see text]) into NO and elicit positive vascular effects. Aims: We aimed to test the effects of oral inorganic [Formula: see text] and vitamin C co-supplementation on vascular function, muscular strength, and on concentrations of urinary [Formula: see text], vitamin C, 8-isoprostanes and salivary [Formula: see text] in healthy young adults. Methods: Ten young healthy participants were enrolled in a randomised, double-blind (only for the [Formula: see text] intervention) crossover clinical trial. Participants consumed in random order: 1) nitrate-rich beetroot juice and vitamin C (N+VC), 2) nitrate-rich beetroot juice alone (N) or 3) nitrate-depleted beetroot juice alone (ND). Resting blood pressure (BP) was measured at the research centre and at home. Non-invasive, continuous measurements of BP and cardiac function parameters were performed using a Finometer device. Free-living physical activity and hand-grip strength were assessed. Salivary [Formula: see text] and [Formula: see text] and urinary [Formula: see text], 8-isoprostanes and vitamin C concentrations were measured. Results: There were no significant differences for any of the vascular outcomes between the three interventions groups. However, analyses of within-intervention changes showed a significant lower daily systolic BP in the [Formula: see text]+vitamin C (N+VC) group only (P=0.04). Urinary [Formula: see text] (P=0.002) and salivary [Formula: see text] (P=0.001) were significantly higher in the N+VC group compared to the N and ND groups. Conclusion: These preliminary findings suggest that combining dietary [Formula: see text] with vitamin C could have protective effects on vascular function in young adults and could represent an effective strategy for the maintenance of healthy cardiovascular trajectories.

Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomised clinical trials.

Results from randomised controlled trials (RCTs) testing the effect of vitamin C supplementation on blood pressure (BP) have been inconsistent. This systematic review evaluated the effects of vitamin C supplementation on BP and included RCTs testing the effects of vitamin C supplementation alone, on systolic and diastolic BP in adult participants (≥18 years). Random-effect models were conducted to estimate the pooled effects of vitamin C supplementation on BP. A total of 20 studies with 890 participants were included. The median dose of vitamin C was 757.5 mg/d, the median duration was 6 weeks. Vitamin C supplementation was found to reduce systolic BP by -3.0 mmHg (95%CI: -4.7, -1.3 mmHg; p = 0.001). Subgroup analysis showed a more pronounced effect on systolic BP in patients with hypertension (-3.2 mmHg, 95%CI -5.2, -1.2 mmHg, p = 0.002) and diabetes (-4.6 mmHg, 95%CI -8.9, -0.3 mmHg, p = 0.03). Further research needs to evaluate the long-term effect of vitamin C on BP in populations with impaired cardio-metabolic health.

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.

Ageing modifies acute resting blood pressure responses to incremental consumption of dietary nitrate: a randomised, cross-over clinical trial.

Beetroot (BR) is a rich source of nitrate (NO3-) that has been shown to reduce blood pressure (BP). Yet, no studies have examined the vascular benefits of BR in whole-food form and whether the effects are modified by age. This study was a four-arm, randomised, open-label, cross-over design in twenty-four healthy adults (young n 12, age 27 ± 4 years, old n 12, age 64 ± 5 years). Participants consumed whole-cooked BR at portions of (NO3- content in brackets) 100 g (272 mg), 200 g (544 mg) and 300 g (816 mg) and a 200-ml solution containing 1000 mg of potassium nitrate (KNO3) on four separate occasions over a 4-week period (≥7-d washout period). BP, plasma NO3- and nitrite (NO2-) concentrations, and post-occlusion reactive hyperaemia via laser Doppler, were measured pre- and up to 5-h post-intervention. Data were analysed by repeated-measures ANOVA. Plasma NO2- concentrations were higher in the young v. old at baseline and post-intervention (P < 0·05). All NO3- interventions decreased systolic and diastolic BP in young participants (P < 0·05), whereas only KNO3 (at 240-300 min post-intake) significantly decreased systolic (-4·8 mmHg, -3·5 %, P = 0·024) and diastolic (-5·4 mmHg, -6·5 %, P = 0·007) BP in older participants. In conclusion, incremental doses of dietary NO3- reduced systolic and diastolic BP in healthy young adults whereas in the older group a significant decrease was only observed with the highest dose. The lower plasma NO2- concentrations in older participants suggest that there may be mechanistic differences in the production of NO from dietary NO3- in young and older populations.

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.

Double-blind controlled dietary cross-over intervention with differentially fertilised intact lettuce leaves shows acute reduction in blood pressure in young adults, associated with faster uptake of nitrate than of phenolics.

PURPOSE: To compare acute effects on blood pressure (BP) of ingestion of visually similar lettuce with controlled high and low content of either nitrate or phenolic compounds. METHODS: In a randomised cross-over design, 19 healthy participants (22-31 years) received 50 g of lettuce containing either 530 mg (8.4 mmol) nitrate + 11 mg (0.03 mmol) phenolic compounds (HNLP); or 3 mg nitrate (0.05 mmol) + 77 mg (0.2 mmol) phenolic compounds (LNHP), obtained by differential fertilisation. Ambulatory BP was recorded along with plasma, salivary and urinary nitrate and nitrite and plasma concentrations of cyclic guanosine monophosphate (cGMP), phenolic metabolites, Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). RESULTS: Compared with LNHP, 3 h post ingestion of HNLP, plasma nitrate increased 0.31 ± (95%CI) 0.12 mM (+ 240%), and salivary nitrate 5.5 ± 1.4 mM (+ 910%); accumulated urinary nitrate excretion increased 188 ± 72 mg (+ 296%) (all P < 0.001). Systolic BP was reduced 4.9 ± 4.2 mmHg (P = 0.031) between 3 and 6 h after ingestion of HNLP compared with LNHP; systolic BP differences were negatively correlated (P = 0.004) with differences in saliva nitrate concentrations. LNHP increased plasma phenolics at 6 h, predominantly 3'-methoxycinnamic acid-4'-glucuronide (ferulic acid-4'-glucuronide), 116%, 204 ± 138 nM more than HNLP (P = 0.001); increased cGMP 14% (P = 0.019); and reduced FRAP 3.1% (P = 0.009). CONCLUSION: The acute BP difference within 6 h of consumption matched the plasma/saliva nitrate peak, not the slower changes of plasma phenolics. This is the first double-blind controlled dietary intervention demonstrating differential effects on human physiology by consumption of an intact plant food, where compositional differences were obtained by controlling growing conditions, indicating potential opportunities for health claims relating to precision/vertical farming. CLINICAL TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov, with identifier NCT02701959, on March 8, 2016.

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.

Association of Dietary Intakes and Genetically Determined Serum Concentrations of Mono and Poly Unsaturated Fatty Acids on Chronic Kidney Disease: Insights from Dietary Analysis and Mendelian Randomization.

Polyunsaturated fatty acid (PUFA) intake is generally associated with better renal function, while the association of monounsaturated fatty acids (MUFAs) remains unconfirmed. Mendelian randomization (MR) analysis was used to obtain unconfounded estimates of the causal association of dietary intake and genetically determined serum PUFA and MUFA levels with measures of renal function. Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were used. Data from the largest genome-wide association studies (GWAS) on MUFAs, PUFAs, eGFR, and chronic kidney disease (CKD) were analysed for the entire sample. A total of 16,025 participants were included. eGFR improved across increasing quartiles of total PUFA intake from 86.3 ± 0.5 (Q1) to 96.2 ± 0.5 mL/min/1.73 m² (Q4), (p < 0.001). Conversely, there was no association between MUFA intake and measures of renal function (all p > 0.21). In multivariable models, the top quartile of PUFA intake had a 21% lower risk for CKD, but there was no significant association between CKD risk and MUFA intake. Genetically determined serum MUFA (heptadecenoate (17:1), myristoleic acid (14:1), and palmitoleic acid (16:1)) and PUFA (α-linolenic acid and eicosapentaenoic acid) concentrations had no significant association with eGFR and CKD risk. Additionally, no association was found in the analyses stratified by diabetes status. Higher dietary PUFA intake is associated with lower risk of CKD, while there was no association with serum levels of MUFAs or PUFAs. Additional studies including clinical trials are warranted.

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.

Nutritional interventions for the prevention of cognitive impairment and dementia in developing economies in East-Asia: a systematic review and meta-analysis.

Dementia represents a key impending global health challenge. The aim of this systematic review was to evaluate the current evidence on nutritional interventions for the prevention of dementia in developing economies in East-Asia. Four comprehensive databases were searched from inception until January 2020: MEDLINE, Embase, PsycInfo, and Scopus. The search was restricted to randomized controlled trials [RCTs] in adult humans, assessing the effect of nutritional interventions on global and domain specific cognitive performance and dementia risk. Meta-analysis of data was conducted for each domain and sub-categorized according to the type of nutritional intervention. Twenty-four RCTs were included, of which, fifteen studies showed significant beneficial effects on cognition. Eighteen studies were included in the meta-analysis. Significant beneficial effects were found for essential fatty acids (EPA/DHA) and micronutrient supplementation on specific cognitive domains including attention and orientation, perception, verbal functions and language skills. The effect size of the interventions appeared to be greater in older subjects with cognitive impairment. Supplementation with B-vitamins and essential fatty acids may represent promising strategies to minimize age-related cognitive decline in Asian populations. Large, high-quality, long-term trials are needed to confirm these findings.

Pharmacokinetic Profile of Incremental Oral Doses of Dietary Nitrate in Young and Older Adults: A Crossover Randomized Clinical Trial.

BACKGROUND: Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. OBJECTIVES: We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. METHODS: Twelve young (18-35 y old) and 12 older (60-75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. RESULTS: Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO3 consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). CONCLUSIONS: BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems.This trial was registered at www.isrctn.com as ISRCTN86706442.

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.

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).

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.

Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: an umbrella review of systematic reviews and meta-analyses.

Vitamin C is an essential nutrient with important antioxidant properties. Higher vitamin C intake appears to be associated with positive effects on cardiovascular risk factors in cohort studies, whereas large randomized controlled clinical trials did not confirm the benefits of supplemental vitamin C on cardiovascular disease (CVD) outcomes. In this overview of systematic reviews and meta-analyses, an "umbrella review," we investigated the effects of vitamin C supplementation on biomarkers of cardiovascular risk, that is, arterial stiffness, blood pressure, endothelial function, glycemic control, and lipid profile. In addition, we assessed the strength of the evidence and the methodological qualities of available studies. Two independent investigators searched 4 databases (Medline, Embase, Scopus, and The Cochrane Library databases) from inception until February 2018. After full text examination, 10 systematic reviews and meta-analyses were included in the umbrella review which included 6409 participants. Three systematic reviews investigated the effects of vitamin C on endothelial function with contrasting results (2 reviews reported a significant effect, and all 3 showed a high heterogeneity [I2> 50%]); 1 systematic review reported significant improvement for each of the following risk factors: blood pressure, and blood concentrations of glucose, low-density lipoprotein cholesterol, and triglycerides. There were no overall effects of vitamin C on arterial stiffness and blood concentration of insulin, total cholesterol, and high-density lipoprotein cholesterol, but subgroup analyses revealed some evidence for significant improvements in subpopulations with higher body mass index, higher plasma concentrations of glucose or cholesterol, and low plasma concentration of vitamin C. Results from this umbrella review emphasize the weakness of the current evidence base about effects of vitamin C supplementation on markers of CVD risk. There is limited evidence that some population subgroups (older people, the obese, those with lower vitamin C status at baseline, and those at higher CVD risk) may be more responsive to vitamin C supplementation and offer opportunities for tailored nutritional interventions to improve cardiometabolic health. Future studies should implement a selective recruitment strategy that is informed by evidence-based literature synthesis.