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Background/Objectives: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks of PD include Lewy bodies and mechanisms like oxidative/nitrosative stress, chronic inflammation, and mitochondrial dysfunction. Nitric oxide (NO), produced by nitric oxide synthase (NOS) isoforms, plays a dual role in neuroprotection and neurodegeneration. Excessive NO production exacerbates neuroinflammation and oxidative/nitrosative damage, contributing to dopaminergic cell death. This review explores NO's role in PD pathogenesis and investigates dietary nitrate as a therapeutic strategy to regulate NO levels. Methods: A literature review of studies addressing the role of NO in PD was conducted using major scientific databases, including PubMed, Scopus, and Web of Science, using keywords such as "nitric oxide", "NOSs", "Parkinson's disease", and "nitrate neuroprotection in PD". Studies on nitrate metabolism via the nitrate–nitrite–NO pathway and its effects on PD hallmarks were analyzed. Studies regarding the role of nitrosamine formation in PD, which are mainly formed during the nitrification process of amines (nitrogen-containing compounds), often due to chemical reactions in the presence of nitrite or nitrate, were also examined. In particular, nitrate has been shown to induce oxidative stress, affect the mitochondrial function, and contribute to inflammatory phenomena in the brain, another factor closely related to the pathogenesis of PD. Results: Excessive NO production, particularly from iNOS and nNOS, was strongly associated with neuroinflammation and oxidative/nitrosative stress, amplifying neuronal damage in PD. Dietary nitrate was shown to enhance NO bioavailability through the nitrate–nitrite–NO pathway, mitigating inflammation and oxidative/nitrosative damage. Conclusions: Dysregulated NO production contributes significantly to PD progression via inflammatory and oxidative/nitrosative pathways. Dietary nitrate, by modulating NO levels, offers a promising therapeutic strategy to counteract these pathological mechanisms. Further clinical trials are warranted to establish its efficacy and optimize its use in PD management. [ABSTRACT FROM AUTHOR]

Objectives: This cohort study investigated the possible association of dietary nitrate (NO3)/nitrite (NO2) intake and risk of progression to type 2 diabetes (T2D) across different phenotypes of prediabetes (Pre-DM). Methods: A total of 1586 adults diagnosed with Pre-DM [i.e., 60.2% isolated impaired fasting glucose (iIFG), 21% isolated impaired glucose tolerance (iIGT), and 18.8% combined IFG-IGT] in the third (2006–2008) and fourth (2009–2011) examinations of the Tehran Lipid and Glucose Study, were assessed for dietary intake of NO3 and NO2 and were followed up to 2015–2017. Cox proportional hazard models, stratified by Pre-DM phenotypes, were used to plot cumulative hazard curve and calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing T2D across tertile categories and per every 100 mg/d NO3 and 2 mg/d NO2 intake exceeded the acceptable daily intake (ADI). Results: The mean age of the participants was 47.2 ± 12.9 years at baseline, and 52.2% were men. Highest intake of NO3 (≥ 645 vs. < 451 mg/d) and NO2 (≥ 11.5 vs. <9.0 mg/d) increased risk of T2D among subjects with iIFG (HR = 1.69, 95% CI = 1.04–2.74 and HR = 2.07, 95% CI = 1.29–3.32). The cumulative hazards were higher in the highest compared to the lowest NO3 and NO2 intake in subjects with iIFG phenotype. Every 100 mg/d of NO3 and 2 mg/d NO2 intake exceeded ADI was associated with an increased risk of progression from iIFG to T2D by 13 and 25%, respectively. Conclusion: High exposure to dietary NO3 and NO2 may be a risk factor for developing T2D in subjects with iIFG. [ABSTRACT FROM AUTHOR]

Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO3−)–nitrite (NO2−)–nitric oxide (NO) pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BRnitrate 600 mg NO3−/140 mL, BRplacebo ∼ 0 mg/140 mL) would improve resting endothelial function and resistance to ischemia–reperfusion (IR) injury to a greater extent in early-postmenopausal (1–6 years following their final menstrual period (FMP), n = 12) compared to late-postmenopausal (6+ years after FMP, n = 12) women. Analyses with general linear models revealed a significant (p < 0.05) time*treatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BRplacebo (early FMD 2.51 ± 1.18%, late FMD 1.30 ± 1.10, p < 0.001) and was lower than post-IR with BRnitrate (early FMD 3.84 ± 1.21%, late FMD 3.21 ± 1.13%, p = 0.014). A single dose of BRnitrate significantly increased resting macrovascular function in the late postmenopausal group only (p = 0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury. [ABSTRACT FROM AUTHOR]

Dietary inorganic nitrate lowers blood pressure (BP) in healthy individuals through improved nitric oxide (NO) bioavailability. However, there is limited evidence examining the long-term effects of dietary nitrate for managing hypertension. We aimed to determine whether the sustained intake of dietary nitrate improved BP and cardiovascular disease (CVD) risk factors in individuals with early-stage hypertension. The Dietary Nitrate (NO3) on BP and CVD Risk Factors (DINO3) Trial was a multi-center, double-blinded, parallel, randomized, controlled trial in participants with elevated BP. Participants were supplemented with high-nitrate (HN) (~400 mg nitrate) or low-nitrate (LN) vegetable powder (~50 mg nitrate) on top of their usual diets for 16 weeks. The primary outcome was office systolic BP at 16 weeks. The secondary outcomes were 24 h ambulatory BP, central BP, heart-rate-corrected augmentation index (AIx75), carotid–femoral pulse wave velocity (cf-PWV), lipids, and high-sensitivity C-reactive protein (hs-CRP). Sixty-six participants were randomized at baseline (39M:27F, age: 51.5 ± 10.8 years, BMI:27.9 ± 3.2 kg/m2). In an intention-to-treat analysis, no differences were observed between HN and LN groups in terms of office systolic BP at 16 weeks (3.91 ± 3.52 mmHg, p = 0.27) or secondary outcomes. In this exploratory study, sustained HN vegetable supplementation did not exhibit more favorable vascular effects than LN vegetable supplementation in individuals with elevated BP. [ABSTRACT FROM AUTHOR]

AbstractInterest in the role of dietary nitrate in human health and disease has grown exponentially in recent years. However, consensus is yet to be reached as to whether consuming nitrate from various food sources is beneficial or harmful to health. Global authorities continue to recommend an acceptable daily intake (ADI) of nitrate of 3.7 mg/kg-bw/day due to concerns over its carcinogenicity. This is despite evidence showing that nitrate consumption from vegetable sources, exceeding the ADI, is associated with decreased cancer prevalence and improvements in cardiovascular, oral, metabolic and neurocognitive health. This review examines the paradox between dietary nitrate and health and disease and highlights the key role of the dietary source and food matrix in moderating this interaction. We present mechanistic and epidemiological evidence to support the notion that consuming vegetable-derived nitrate promotes a beneficial increase in nitric oxide generation and limits toxic N-nitroso compound formation seen with high intakes of nitrate added during food processing or present in contaminated water. We demonstrate the need for a more pragmatic approach to nitrate-related nutritional research and guidelines. Ultimately, we provide an overview of our knowledge in this field to facilitate the various therapeutic applications of dietary nitrate, whilst maintaining population safety. [ABSTRACT FROM AUTHOR]

Physical inactivity and poor dietary choices contribute to the rise in cardiometabolic diseases in the United States. It remains critical to identify strategies that may mitigate the negative impact of these behaviors. Several studies have shown that the consumption of dietary inorganic nitrate may improve vascular health and glucose regulation in animal models and some human studies. However, the improvements in glucose regulation have yet to be corroborated in humans with type 2 diabetes (T2D). Therefore, the purpose of this study was to assess the acute effects of beetroot juice (BRJ) on glycemic and hemodynamic responses in individuals with T2D while controlling for medication. Seven participants with a clinical diagnosis of T2D were recruited into this study and were temporarily removed from blood pressure- and glucose-lowering medications. Hemodynamic measurements (pulsewave velocity) and an oral glucose tolerance test (glycemic response) were measured following consumption of either BRJ or a denitrolized placebo. Saliva and blood samples were collected at baseline and two and four hours post supplementation to measure changes in nitrate and nitrite concentrations. We detected significant improvements in total plasma glucose exposure (p = 0.022) and the SVR change score (p = 0.009) in the BRJ condition. This study demonstrated that BRJ consumption can improve oral glucose tolerance in individuals with T2D while controlling for medication; however, future larger-cohort randomized controlled trials are needed to confirm if BRJ is a viable treatment for glucose control in individuals with T2D. [ABSTRACT FROM AUTHOR]

Despite recent interest in functional food merits of dietary nitrate, there is a paucity of information on its utility as a pre-biotic for the enrichment of health-promoting oral bacteria. The objective of this investigation was to observe the dynamic change in the denitrifying oral microbiome of healthy human volunteers following supplementation of nitrate enriched diet for a period of two-weeks. The study involved isolation, identification and comparison of nitrate-reducing oral bacteria of five human volunteers before and after supplementation of a nitrate-rich diet. This was further correlated with salivary nitrite contents to understand denitrification efficacy with prolonged dietary nitrate supplementation. A total of 153 bacterial strains were isolated from baseline (BSL) samples of healthy participants, i.e. before supplementation and after dietary nitrate supplementation (ADNS); 32 out of these isolates could be confirmed to be nitrate-reducers. Although members of Firmicutes viz., Streptococcus salivarius, Streptococcus parasanguinis and Actinobacteria viz., Rothia mucilaginosa were present in both BSL and ADNS samples, the relative abundance of Actinobacteria was higher and Firmicutes was lower in ADNS in comparison to BSL samples. Moreover, Proteobacteria were found only in ADNS and not BSL samples. Interestingly, these changes in nitrate-reducing microbiome were correlated with higher salivary nitrite levels on day 14 in comparison to day 1 following acute supplementation of dietary NO3−. Thus, it is being hypothesized that Rothia, Neisseria and Streptococcus spp. which appeared following 14 days of nitrate supplementation, could be more efficient towards reducing nitrate and boosting salivary nitrite levels. [ABSTRACT FROM AUTHOR]

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

Nitrate (NO3−) obtained from the diet is converted to nitrite (NO2−) and subsequently to nitric oxide (NO) within the body. Previously, we showed that porcine eye components contain substantial amounts of nitrate and nitrite that are similar to those in blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. To gain deeper insights into nitrate metabolism in porcine eyes, our current study involved feeding pigs either NaCl or Na15NO3 and assessing the levels of total and 15N-labeled NO3−/NO2− in various ocular tissues. Three hours after Na15NO3 ingestion, a marked increase in 15NO3− and 15NO2− was observed in all parts of the eye; in particular, the aqueous and vitreous humor showed a high 15NO3− enrichment (77.5 and 74.5%, respectively), similar to that of plasma (77.1%) and showed an even higher 15NO2− enrichment (39.9 and 35.3%, respectively) than that of plasma (19.8%). The total amounts of NO3− and NO2− exhibited patterns consistent with those observed in 15N analysis. Next, to investigate whether nitrate or nitrite accumulate proportionally after multiple nitrate treatments, we measured nitrate and nitrite contents after supplementing pigs with Na15NO3 for five consecutive days. In both 15N-labeled and total nitrate and nitrite analysis, we did not observe further accumulation of these ions after multiple treatments, compared to a single treatment. These findings suggest that dietary nitrate supplementation exerts a significant influence on nitrate and nitrite levels and potentially NO levels in the eye and opens up the possibility for the therapeutic use of dietary nitrate/nitrite to enhance or restore NO levels in ocular tissues. [ABSTRACT FROM AUTHOR]

The generation of nitrite by the oral microbiota is believed to contribute to healthy cardiovascular function, with oral nitrate reduction to nitrite associated with systemic blood pressure regulation. There is the potential to manipulate the composition or activities of the oral microbiota to a higher nitrate-reducing state through nitrate supplementation. The current study examined microbial community composition and enzymatic responses to nitrate supplementation in sessile oral microbiota grown in continuous culture. Nitrate reductase (NaR) activity and nitrite concentrations were not significantly different to tongue-derived inocula in model biofilms. These were generally dominated by Streptococcus spp., initially, and a single nitrate supplementation resulted in the increased relative abundance of the nitrate-reducing genera Veillonella, Neisseria, and Proteus spp. Nitrite concentrations increased concomitantly and continued to increase throughout oral microbiota development. Continuous nitrate supplementation, over a 7-day period, was similarly associated with an elevated abundance of nitratereducing taxa and increased nitrite concentration in the perfusate. In experiments in which the models were established in continuous low or high nitrate environments, there was an initial elevation in nitrate reductase, and nitrite concentrations reached a relatively constant concentration over time similar to the acute nitrate challenge with a similar expansion of Veillonella and Neisseria. In summary, we have investigated nitrate metabolism in continuous culture oral biofilms, showing that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of putatively NaR-producing taxa. IMPORTANCE Clinical evidence suggests that blood pressure regulation can be promoted by nitrite generated through the reduction of supplemental dietary nitrate by the oral microbiota. We have utilized oral microbiota models to investigate the mechanisms responsible, demonstrating that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of nitrate-reducing taxa. [ABSTRACT FROM AUTHOR]

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

Abstract Dementia is a highly prevalent and costly disease characterised by deterioration of cognitive and physical capacity due to changes in brain function and structure. Given the absence of effective treatment options for dementia, dietary and other lifestyle approaches have been advocated as potential strategies to reduce the burden of this condition. Maintaining an optimal nutritional status is vital for the preservation of brain function and structure. Several studies have recognised the significant role of nutritional factors to protect and enhance metabolic, cerebrovascular, and neurocognitive functions. Caloric restriction (CR) positively impacts on brain function via a modulation of mitochondrial efficiency, endothelial function, neuro-inflammatory, antioxidant and autophagy responses. Dietary nitrate, which serves as a substrate for the ubiquitous gasotransmitter nitric oxide (NO), has been identified as a promising nutritional intervention that could have an important role in improving vascular and metabolic brain regulation by affecting oxidative metabolism, ROS production, and endothelial and neuronal integrity. Only one study has recently tested the combined effects of both interventions and showed preliminary, positive outcomes cognitive function. This paper explores the potential synergistic effects of a nutritional strategy based on the co-administration of CR and a high-nitrate diet as a potential and more effective (than either intervention alone) strategy to protect brain health and reduce dementia risk.

Nitrate supplementation has been studied as a beneficial constituent of the human diet, particularly for its effects on vascular health through vasodilation. Recent studies have focused on the benefits of nitrate supplementation in animals, especially in swine. Up to 1,200 mg/kg dietary nitrate supplementation from Ca nitrate was beneficial in farrowing and lactating sows and their offspring, and up to 6,000 mg/kg supplemental nitrate showed no adverse health effects in sows or piglets. Controlled study data evaluating the safety of nitrate supplementation to growing swine of any weight class is scant. Therefore, an experiment was conducted to test the hypothesis that increased inclusion rates of dietary nitrate through the addition of Ca nitrate in diets would not influence concentrations of nitrate or nitrite in serum and tissue, nor blood hemoglobin and methemoglobin. Forty-eight individually housed pigs (initial weight 119.1 ± 5.3 kg) were randomly allotted to four dietary treatments containing 0, 500, 1,000, or 2,000 mg/kg dietary nitrate and fed experimental diets for 28 d. Growth performance was not influenced (P  > 0.10) by dietary treatment. The most sensitive safety endpoint, methemoglobin, did not change (P  > 0.10) with dietary nitrate exposure up to 2,000 mg/kg. Serum and tissue nitrate and nitrite levels, myoglobin, and hemoglobin were not adversely affected (P  > 0.10). Total myoglobin in the loin linearly increased (P  < 0.05) with greater dietary nitrate in the diet, which is correlated with the red color of meat. This work established the safety of up to 2,000 mg/kg dietary nitrate from Ca nitrate as an ingredient in food for finishing pigs. [ABSTRACT FROM AUTHOR]

This mini-review summarizes the comparative effects of different sources of dietary nitrate (NO3−), beetroot juice (BRJ) and nitrate salts (NIT), on physiological function and exercise capacity. Our objectives were to determine whether BRJ is superior to NIT in enhancing exercise-related outcomes, and to explore the potential contribution of other putatively beneficial compounds in BRJ beyond NO3−. We conducted a comparative analysis of recent studies focused on the impact of BRJ versus NIT on submaximal oxygen consumption (VO2), endurance performance, adaptations to training, and recovery from muscle-damaging exercise. While both NO3− sources provide benefits, there is some evidence that BRJ may offer additional advantages, specifically in reducing VO2 during high-intensity exercise, magnifying performance improvements with training, and improving recovery post-exercise. These reported differences could be due to the hypothesized antioxidant and/or anti-inflammatory properties of BRJ resulting from the rich spectrum of phytonutrients it contains. However, significant limitations to published studies directly comparing BRJ and NIT make it quite challenging to draw any firm conclusions. We provide recommendations to help guide further research into the important question of whether there is more to the story of BRJ than just NO3−.

Abstract Objective: Evaluate knowledge and beliefs about dietary nitrate among United Kingdom (UK)-based adults. Design: An online questionnaire was administered to evaluate knowledge and beliefs about dietary nitrate. Overall knowledge of dietary nitrate was quantified using a twenty-one-point Nitrate Knowledge Index. Responses were compared between socio-demographic groups. Setting: UK. Participants: A nationally representative sample of 300 adults. Results: Only 19 % of participants had heard of dietary nitrate prior to completing the questionnaire. Most participants (∼70 %) were unsure about the effects of dietary nitrate on health parameters (e.g. blood pressure, cognitive function and cancer risk) or exercise performance. Most participants were unsure of the average population intake (78 %) and acceptable daily intake (83 %) of nitrate. Knowledge of dietary sources of nitrate was generally low, with only ∼30 % of participants correctly identifying foods with higher or lower nitrate contents. Almost none of the participants had deliberately purchased, or avoided purchasing, a food based around its nitrate content. Nitrate Knowledge Index scores were generally low (median (interquartile range (IQR)): 5 (8)), but were significantly higher in individuals who were currently employed v. unemployed (median (IQR): 5 (7) v. 4 (7); P < 0·001), in those with previous nutrition education v. no nutrition education (median (IQR): 6 (7) v. 4 (8); P = 0·012) and in individuals who had heard of nitrate prior to completing the questionnaire v. those who had not (median (IQR): 9 (8) v. 4 (7); P < 0·001). Conclusions: This study demonstrates low knowledge around dietary nitrate in UK-based adults. Greater education around dietary nitrate may be valuable to help individuals make more informed decisions about their consumption of this compound.

The authors examine the effect of an acute dose of beetroot juice on endurance running performance in "real-world" competitive settings. In total, 70 recreational runners (mean ± SD: age = 33.3 ± 12.3 years, training history = 11.9 ± 8.1 years, and hours per week training = 5.9 ± 3.5) completed a quasi-randomized, double-blind, placebo-controlled study of 5-km competitive time trials. Participants performed four trials separated by 1 week in the order of prebaseline, two experimental, and one postbaseline. Experimental trials consisted of the administration of 70-ml nitrate-rich beetroot juice (containing -4.1 mmol of nitrate, Beet It Sport®) or nitrate-depleted placebo (containing -0.04 mmol of nitrate, Beet It Sport®) 2.5 hr prior to time trials. Time to complete 5 km was recorded for each trial. No differences were shown between pre- and postbaseline (p = .128, coefficient variation = 2.66%). The average of these two trials is therefore used as baseline. Compared with baseline, participants ran faster with beetroot juice (mean differences = 22.2 ± 5.0 s, p < .001, d = 0.08) and placebo (22.9 ± 4.5 s, p < .001, d = 0.09). No differences in times were shown between beetroot juice and placebo (0.8 ± 5.7 s, p < .875, d = 0.00). These results indicate that an acute dose of beetroot juice does not improve competitive 5-km time-trial performance in recreational runners compared with placebo. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). Methods: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P 0.80. Discussion: The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future ‘pivotal’, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.

Dementia is a highly prevalent and costly disease characterised by deterioration of cognitive and physical capacity due to changes in brain function and structure. Given the absence of effective treatment options for dementia, dietary and other lifestyle approaches have been advocated as potential strategies to reduce the burden of this condition. Maintaining an optimal nutritional status is vital for the preservation of brain function and structure. Several studies have recognised the significant role of nutritional factors to protect and enhance metabolic, cerebrovascular, and neurocognitive functions. Caloric restriction (CR) positively impacts on brain function via a modulation of mitochondrial efficiency, endothelial function, neuro-inflammatory, antioxidant and autophagy responses. Dietary nitrate, which serves as a substrate for the ubiquitous gasotransmitter nitric oxide (NO), has been identified as a promising nutritional intervention that could have an important role in improving vascular and metabolic brain regulation by affecting oxidative metabolism, ROS production, and endothelial and neuronal integrity. Only one study has recently tested the combined effects of both interventions and showed preliminary, positive outcomes cognitive function. This paper explores the potential synergistic effects of a nutritional strategy based on the co-administration of CR and a high-nitrate diet as a potential and more effective (than either intervention alone) strategy to protect brain health and reduce dementia risk. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that acute ingestion of inorganic nitrate (NO 3 −)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO 3 − → nitrite (NO 2 −) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO 3 − increased plasma NO 3 − and NO 2 − concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO 3 − and NO 2 − levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO 3 − supplementation. We conclude that both acute and short-term dietary NO 3 − supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant. • The effects of beetroot juice (BRJ) were determined in 16 older men and women. • Acute ingestion of NO 3 −-containing BRJ increased muscle power by 7 ± 13% (P = 0.0088). • Daily ingestion for 2 wk increased muscle power by 9 ± 11% (P = 0.0038). • BRJ ± NO 3 − did not alter blood pressure or plasma markers of oxidative stress. • Acute and short-term NO 3 − supplementation have equal effects on muscle function. [ABSTRACT FROM AUTHOR]

The acute effects of maltodextrin (MD) ingestion combined with dietary nitrate (NO3-) on running economy (RE), substrate oxidation, and muscle oxygenation during running were investigated. Ten male marathon runners participated in a double-blind crossover design, receiving either 1.5 g MD·kg-1 BM (MD) or an isocaloric co-ingestion of 1.5 g MD·kg-1 BM and 500 mg NO3-beverage (MDNO). Measurements were taken at various stages to assess RE, followed by a 60-minute run at 70% of VO2 peak. The results showed no significant differences in RE, substrate oxidation, or muscle oxygenation between MD and MDNO. However, the respiratory exchange ratio (RER) was significantly lower during high-intensity prolonged running following MDNO compared to MD. In conclusion, acute co-ingestion of MD with dietary NO3- may impact aerobic energy production but does not significantly affect RE or muscle oxygenation during high-intensity prolonged running. [ABSTRACT FROM AUTHOR]

Nitrate was once thought to be an inert end-product of endothelial-derived nitric oxide (NO) heme oxidation; however, this view has been radically revised over the past few decades. Following the clarification of the nitrate-nitrite-NO pathway, accumulated evidence has shown that nitrate derived from the diet is a supplementary source of endogenous NO generation, playing important roles in a variety of pathological and physiological conditions. However, the beneficial effects of nitrate are closely related with oral health, and oral dysfunction has an adverse effect on nitrate metabolism and further impacts overall systemic health. Moreover, an interesting positive feedback loop has been identified between dietary nitrate intake and oral health. Dietary nitrate's beneficial effect on oral health may further improve its bioavailability and promote overall systemic well-being. This review aims to provide a detailed description of the functions of dietary nitrate, with an emphasis on the key role oral health plays in nitrate bioavailability. This review also provides recommendations for a new paradigm that includes nitrate therapy in the treatment of oral diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3−)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤ 0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3−) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3− were associated with reduced brachial systolic BP (ρ = −0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.

The effects of nitrate-rich beetroot extract (BRE) on blood pressure (BP) indices and intense intermittent exercise performance have yet to be examined. To investigate the short-term (5-day) effects of BRE supplementation on resting blood pressure (BP), nitric oxide (NO) bioavailability, blood hemoglobin, blood glucose, cognitive task (Stroop test), and intense intermittent exercise performance (Yo-Yo Intermittent Recovery Level 1 test; YYIRTL1) performance. In a double-blind, randomized, crossover manner, 18 healthy males received beetroot extract (BRE; 500 mg·kg-1·day-1) and placebo (PLA) for 5 days, with a washout period of 10 days separating each trial. The total length covered in the YYIRTL1 was not statistically different during the BRE (783 ± 388 m) compared to the PLA (737 ± 357 m) trial (P > 0.05). Systolic blood pressure was lower in the beetroot extract condition (BRE: 113 ± 12 mmHg) compared to the placebo (PLA: 122 ± 12 mmHg) and control (CON: 123 ± 12 mmHg) conditions (P < 0.05), with no significant main effect for supplementation for diastolic blood pressure (P > 0.05). Mean arterial pressure was reduced in the BRE condition (88 ± 3 mmHg) compared to the placebo (PLA: 92 ± 2 mmHg). Performance in the Stroop test was ~9.53% and ~ 8.45% faster at rest and during YYIRTL1 with BRE compared to PLA, respectively. The current results indicate short-term nitrate-rich supplements, in a form of beetroot extract, may not be ergogenic for intense intermittent exercise as the supplementation failed to improve intense intermittent exercise performance. Nevertheless, short-term BRE intake can be a highly practical blood pressure management strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In non-cancer populations, inorganic dietary nitrate (NO3−) supplementation is associated with enhanced cardiorespiratory function but remains untested in patients with a history of cancer. Therefore, this pilot study sought to determine if oral NO3− supplementation, as a supportive care strategy, increases left ventricular (LV) function and exercise performance in survivors of cancer treated with anticancer therapy while simultaneously evaluating the feasibility of the methods and procedures required for future large-scale randomized trials. Two cohorts of patients with a history of cancer treated with anticancer chemotherapy were recruited. Patients in cohort 1 (n = 7) completed a randomized, double-blind, crossover study with 7 days of NO3− or placebo (PL) supplementation, with echocardiography. Similarly, patients in cohort 2 (n = 6) received a single, acute dose of NO3− supplementation or PL. Pulmonary oxygen uptake (VO2), arterial blood pressure, and stroke volume were assessed during exercise. In cohort 1, NO3− improved LV strain rate in early filling (mean difference (MD) [95% CI]: − 0.3 1/s [− 0.6 to 0.06]; P = 0.04) and early mitral septal wall annular velocity (MD [95% CI]: 0.1 m/s [− 0.01 to − 0.001]; P = 0.02) compared to placebo. In cohort 2, NO3− decreased the O2 cost of low-intensity steady-state exercise (MD [95% CI]: − 0.5 ml/kg/min [− 0.9 to − 0.09]; P = 0.01). Resting and steady-state arterial blood pressure and stroke volume were not different between conditions. No differences between conditions for peak VO2 (MD [95% CI]: − 0.7 ml/kg/min [− 3.0 to 1.6]; P = 0.23) were observed. The findings from this pilot study warrant further investigation in larger clinical trials targeting the use of long-term inorganic dietary NO3− supplementation as a possible integrative supportive care strategy in patients following anticancer therapy. [ABSTRACT FROM AUTHOR]

Dementia is a significant public health priority with approximately 55 million cases worldwide, and this number is predicted to quadruple by 2050. Adherence to a healthy diet and achieving optimal nutritional status are vital strategies to improve brain health. The importance of this area of research has been consolidated into the new term 'nutritional psychiatry'. Dietary nitrate, closely associated with the intake of fruits and vegetables, is a compound that is increased in dietary patterns such as the Mediterranean and MIND diets and has protective effects on cognition and brain health. Nitrate is characterised by a complex metabolism and is the precursor of the nitrate–nitrite–nitric oxide (NO) pathway contributing to systemic NO generation. A higher intake of dietary nitrate has been linked to protective effects on vascular outcomes including blood pressure and endothelial function. However, the current evidence supporting the protective effects of dietary nitrate on brain health is less convincing. This article aims to provide a critical appraisal of the current evidence for dietary nitrate supplementation for improving brain health and provide suggestions for future research. [ABSTRACT FROM AUTHOR]

Background and objective: Peak torque, as measured by the gold standard method of isokinetic dynamometry, is affected by consumed of dietary nitrate (NO3-) in the form of beetroot juice (BRJ). The increasing strength performance effect of BRJ has also started to arouse interest in combat sports. This study aims to investigate the effects of acute dietary nitrate supplementation on lower and upper body isokinetic strength of trained Greco-Roman wrestlers. Materials and methods: The study is a double-blind, randomized, crossover design in which eight trained male Greco-Roman wrestlers (21.87 ± 2.3 years; height 176.87 cm ± 4.1 cm; body weight 76.75 kg ± 5.4 kg) consumed beetroot juice (140 mL) or placebo (140 mL, cherry juice with lemon juice) 150 min before performing isokinetic strength. Participants performed knee extensors and flexors and shoulder internal and external rotator isokinetic strength test (in the dominant limbs) concentrically at 60∘ with by Cybex device (Cybex NORM®, Humac, CA, USA). The same trial procedure was repeated with the other supplement (BRJ or Placebo) in a second testing session five days later. BRJ and Placebo trials’ isokinetic strength values were compared with parametric testing (paired sample T-test). Results: Although there was a significant difference in peak torque of shoulder internal and external rotator values in favor of BRJ (P < 0.05), there was no significant difference in the knee strength test. Additionally, all average isokinetic strength values were significantly increased in the BRJ trial (P < 0.05). Conclusions: These results suggest that BRJ can be used as an ergogenic effect for improving strength values in Greco-Roman wrestling.

Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. This bioactive signalling molecule is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate–nitrite–NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in age-matched healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL, 400 mg nitrate) and placebo BJ (70 mL, 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity. [ABSTRACT FROM AUTHOR]

Previous studies suggest that nitric oxide is involved in the regulation of the intraocular pressure (IOP) and in the pathophysiology of open-angle glaucoma (OAG). However, prospective studies investigating the association between dietary nitrate intake, a source of nitric oxide, and incident (i)OAG risk are limited. We aimed to determine the association between dietary nitrate intake and iOAG, and to evaluate the association between dietary nitrate intake and IOP. From 1991 onwards, participants were followed each five years for iOAG in the Rotterdam Study. A total of 173 participants developed iOAG during follow-up. Cases and controls were matched on age (mean ± standard deviation: 65.7 ± 6.9) and sex (%female: 53.2) in a case:control ratio of 1:5. After adjustment for potential confounders, total dietary nitrate intake was associated with a lower iOAG risk (odds ratio (OR) with corresponding 95% confidence interval (95% CI): 0.95 (0.91–0.98) for each 10 mg/day higher intake). Both nitrate intake from vegetables (OR (95% CI): 0.95 (0.91–0.98) for each 10 mg/day higher intake) and nitrate intake from non-vegetable food sources (OR (95% CI): 0.63 (0.41–0.96) for each 10 mg/day higher intake) were associated with a lower iOAG risk. Dietary nitrate intake was not associated with IOP. In conclusion, dietary nitrate intake was associated with a reduced risk of iOAG. IOP-independent mechanisms may underlie the association with OAG. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) control is a key target for interventions to reduce cognitive decline. This cross-sectional study explored associations between objective (24-hour urine excretion) and subjective (food frequency questionnaire [FFQ]) measures of dietary sodium and nitrate intakes with cognitive function and resting BP in the InCHIANTI cohort. Baseline data from 989 participants aged >50 years were included. In fully adjusted models, participants with concurrent high nitrate and low sodium (Odds Ratio (OR)=0.49, 95%CI 0.32–0.76, p = 0.001) and high nitrate and high sodium (OR = 0.49, 95%CI 0.32–0.77, p = 0.002) 24-hour urinary concentrations had lower odds of high BP than participants with low nitrate and high sodium concentrations. We found no significant associations between sodium and nitrate intakes (24-hour urinary concentrations and FFQ) and poor cognitive performance. Urinary nitrate excretion was associated with lower BP and results appeared to be independent of sodium intake. Further analyses in longitudinal studies are required to substantiate these findings. [ABSTRACT FROM AUTHOR]

Progress in understanding physiological mechanisms often consists of discrete discoveries made across different models and species. Accordingly, understanding the mechanistic bases for how altering nitric oxide (NO) bioavailability impacts exercise tolerance (or not) depends on integrating information from cellular energetics and contractile regulation through microvascular/vascular control of O 2 transport and pulmonary gas exchange. This review adopts state-of-the-art concepts including the intramyocyte power grid, the Wagner conflation of perfusive and diffusive O 2 conductances, and the Critical Power/Critical Speed model of exercise tolerance to address how altered NO bioavailability may, or may not, affect physical performance. This question is germane from the elite athlete to the recreational exerciser and particularly the burgeoning heart failure (and other clinical) populations for whom elevating O 2 transport and/or exercise capacity translates directly to improved life quality and reduced morbidity and mortality. The dearth of studies in females is also highlighted, and areas of uncertainty and questions for future research are identified. • We summarize the effects of nitrate(NO 3 −)/nitrite(NO 2 −) supplementation on exercise tolerance in healthy subjects and heart failure patients, starting with the impact of greater nitric oxide (NO) bioavailability on muscle perfusive and diffusive O 2 conductance up to the mechanisms by which nitrate supplementation enhances muscle contractile function • We also explore how the positive effects of elevated intramyocyte NO bioavailability combine with NO-induced cytochrome c oxidase inhibition to better distribute O 2 across the myocyte • Finally, we highlight what little is known regarding sex differences in response to NO 3 − supplementation and identify next-step questions in this vital arena. [ABSTRACT FROM AUTHOR]

Aims: To test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/doxazosin, to control for blood pressure (BP). Methods: A subgroup of participants in our double‐blind, randomized‐controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate‐containing beetroot juice or placebo nitrate‐depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima–media thickness (CIMT, mm) was performed at baseline, 3‐ and 6‐months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed‐model effect, adjusted for confounders. Results: In total, 93 subjects had a baseline evaluation and 86% had follow‐up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate‐containing vs. placebo juice significantly lowered CIMT (−0.06 [95% confidence interval −0.12, −0.01], P =.034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (−0.34 [−0.62, −0.06]) however, no difference was detected vs. spironolactone (−0.15 [−0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD. Conclusions: Our results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP‐independent effect on carotid structure and function. [ABSTRACT FROM AUTHOR]

Background: Previous narrative reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3− on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3− supplementation on human muscle power. Methods: The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov, and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3− on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. Results: Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10− 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10− 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10− 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). Conclusions: Acute or chronic dietary NO3− intake significantly increases maximal muscle power in humans. The magnitude of this effect–on average, ~ 5%–is likely to be of considerable practical and clinical importance. [ABSTRACT FROM AUTHOR]

This study investigated the impact of dietary nitrate supplementation on peripheral hemodynamics, the development of neuromuscular fatigue, and time to task failure during cycling exercise. Eleven recreationally active male participants (27 ± 5 yr, VO2max: 42 ± 2 mL/kg/min) performed two experimental trials following 3 days of either dietary nitrate-rich beetroot juice (4.1 mmol NO3 -/day; DNS) or placebo (PLA) supplementation in a blinded, counterbalanced order. Exercise consisted of constantload cycling at 50, 75, and 100 W (4 min each) and, at -80% of peak power output (218 ± 12 W), to task-failure. All participants returned to repeat the shorter of the two trials performed to task failure, but with the opposite supplementation regime (iso-time comparison; ISO). Mean arterial pressure (MAP), leg blood flow (QL; Doppler ultrasound), leg vascular conductance (LVC), and pulmonary gas exchange were continuously assessed during exercise. Locomotor muscle fatigue was determined by the change in pre to postexercise quadriceps twitch-torque (DQtw) and voluntary activation (DVA; electrical femoral nerve stimulation). Following DNS, plasma [nitrite] (-670 vs. ~180 nmol) and [nitrate] (~775 vs. ~11 µmol) were significantly elevated compared with PLA. Unlike PLA, DNS lowered both QL and MAP by ~8% (P < 0.05), but did not alter LVC (P = 0.31). V O2 across work rates, as well as cycling time to task-failure (~7 min) and locomotor muscle fatigue following the ISO-time comparison were not different between the two conditions (DQtw ~42%, DVA ~4%). Thus, despite significant hemodynamic changes, DNS did not alter the development of locomotor muscle fatigue and, ultimately, cycling time to task failure. [ABSTRACT FROM AUTHOR]

In pigs, nitrate supplements can protect salivary glands from the damage caused by radiation therapy to the head and neck.

Background Previous narrative reviews have concluded that dietary nitrate (NO3 −) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3 − on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3 − supplementation on human muscle power. Methods The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov, and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3 − on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. Results Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge’s g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10− 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10− 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10− 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). Conclusions Acute or chronic dietary NO3 − intake significantly increases maximal muscle power in humans. The magnitude of this effect–on average, ~ 5%–is likely to be of considerable practical and clinical importance.

Background: Postmenopausal women exhibit higher rates of disability and cardiovascular disease (CVD) with aging compared to men. Whereas habitual exercise training is a known strategy to enhance physiologic function in men and premenopausal women, exercise-related adaptations are often modest in postmenopausal women. We propose dietary nitrate (beetroot juice) administered prior to exercise training may be a feasible approach to improve mobility and cardio-metabolic health outcomes in postmenopausal women. Methods: Our randomized, placebo-controlled study aims to determine preliminary effects sizes for changes in functional mobility and endothelium-dependent vasodilation across three study arms: exercise only (EX), exercise + placebo (EX + PL), and exercise + beetroot (EX + BR). Thirty-six postmenopausal women are recruited in small cohorts wherein group exercise is implemented to facilitate social support and adherence to an 8-week training progression. Participants are randomized to one of three study arms (n = 12 per group) following baseline assessments. Post-intervention assessments are used to determine pre-post changes in outcome measures including distance covered during a 6 min walk test, walking economy, muscle speed and power, and endothelial-dependent vasodilation as determined by flow-mediated dilation. Measures of feasibility include recruitment, retention, adherence to exercise prescription, perceived exercise session difficulty, and adverse event rates. Discussion: Evidence-based, translational strategies are needed to optimize exercise training-related adaptations in postmenopausal women. Findings will inform larger randomized clinical trials to determine if pre-exercise consumption of beetroot juice is an efficacious strategy to promote mobility and attenuate CVD disease risk.

Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO 3) to nitrite (NO 2) to NO. The combined effect of vitamin C and NO 3 supplementation is relatively unexplored in untreated hypercholesterolemia. We aimed to examine whether co-administration of vitamin C and nitrate for 4-weeks would improve endothelial function (primary outcome), plasma NO metabolites, oxidative stress, and blood lipids (secondary outcomes). Subjects 50–70 years of age with low density lipoprotein (LDL) > 130 mg/dL and RHI ≤2 were enrolled in this randomized double-blind crossover study. Subjects were assigned to two 4-week supplementation treatments starting with 70 ml of concentrated beetroot juice (CBJ) with 1000 mg of vitamin C (NC) or CBJ with matched placebo (N), then switched to alternate treatment following 2-week washout. The change in reactive hyperemia index (RHI), sum of plasma NO metabolites (NO 2 + NO 3 (NOx)), oxidized LDL (oxLDL), and serum lipids were assessed at baseline and at 4-weeks of each treatment period. Eighteen subjects (11M:7F) completed all study visits. No significant treatment differences were observed in RHI change (N: 0.21 ± 0.12; NC: 0.20 ± 0.17; p = 0.99). Secondary analysis revealed that a subgroup of NC subjects who started with a baseline RHI of <1.67 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >1.67 (1.23 ± 0.15 to 1.96 ± 0.19; n = 8 vs. 1.75 ± 0.11 to 1.43 ± 0.10; n = 8; p = 0.02). Compared to N, NC experienced a significant increase in plasma NOx (N: 94.2 ± 15.5 μmol/L; NC: 128.7 ± 29.1 μmol/L; p = 0.01). Although there was no significant difference in oxLDL change between treatments (N: −1.08 ± 9.8 U/L; NC: −6.07 ± 9.14 U/L; p = 0.19), NC elicited significant reductions in LDL (N: 2.2 ± 2; NC: −10.7 ± 23; p = 0.049), triglycerides (N: 14.6 ± 43; NC: −43.7 ± 45; p = 0.03), and no change in serum high density lipoprotein. Within treatment group comparisons showed that only NC reduced oxLDL significantly from baseline to 4 weeks (p = 0.01). No between intervention differences were observed in RHI. RHI only improved in NC subjects with ED at intervention baseline. Four weeks of NC enriched the NO pool and promoted reduction of blood lipids and oxidative stress in subjects with hypercholesterolemia. These preliminary findings highlight a supplementation strategy that may reduce the progression of atherosclerotic disease and deserves further attention in studies using flow mediated dilation methods. www.clinicaltrials.gov (NCT04283630). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Research suggests that beet juice is beneficial during aerobic exercise. However, the impact of beet juice during primarily anaerobic exercise is equivocal. The purpose of this study was to determine the effects of acute beet juice supplementation on maximal intensity performance during 30-s and 60-s maximal-intensity cycling sprints. Using a double-blind, crossover-study design, 14 anaerobically trained male hockey players completed six Wingate cycling tests: familiarization trials of a 30-s and 60-s Wingate test, followed by 30-s Wingate placebo/beet juice trials, and 60-s Wingate placebo/beet juice trials. Repeated measures ANOVAs were used to compare the change in power between conditions over the duration of each trial. Paired t-tests were run to compare performance between conditions of various work and power variables. One-way ANOVAs were utilized to compare the change between conditions of the 30-s test to the change between conditions of the 60-s test. Beet juice supplementation yielded no statistical differences from placebo in any of the measured variables during the 30-s or 60-s tests (p > 0.05). The percent change for fatigue index was significantly different between the 30-s and 60-s tests (p = 0.032) suggesting less fatigue with beet juice supplementation. Overall, beet juice did not improve maximal intensity performance during 30-s or 60-s cycling sprint tests. Performance during the 60-s bout was not impacted to a greater extent than the 30-s bout after beet juice supplementation. These results suggest that beet juice supplementation does not improve short-duration exercise performance in anaerobically trained athletes. [ABSTRACT FROM AUTHOR]

The current recommendation for reducing person-to-person Coronavirus 2019 (COVID-19) transmission is social distancing, including remote work and school, and home confinement. However, confinement may cause negative feelings, such as frustration, anger, boredom, and stress, in quarantined people. Furthermore, unhealthy diet and physical inactivity behaviors are commonly linked to home confinement, leading to weight gain, metabolic disorders, smoking, and exacerbated alcohol consumption. As a result, these unhealthy behaviors are typically linked to vascular endothelium damage (endothelial dysfunction), which is a first step for the development of cardiovascular disease (CVD). Given that CVD is the main cause of morbidity and mortality worldwide, attenuating the progression of endothelial dysfunction is very important for the control of CVD. Consuming vegetable rich in nitrate, such as beetroots, may be an effective way to prevent endothelial dysfunction. Several emerging studies have recommended beetroot juice in order to improve endothelial function in hypertensive, hypercholesterolemic individuals, as well as in those with CVD risk factors. Therefore, nitrate-rich vegetable consumption, such as beetroot, should be encouraged to be included in the diet during confinement from COVID-19 outbreaks in order to alleviate the potential negative effect of home confinement on cardiovascular health.

Chronic hypertension during gestation is associated with an increased risk of adverse pregnancy outcomes including pre-eclampsia, fetal growth restriction and preterm birth. Research into new chemotherapeutic regimes for the treatment of hypertension in pregnancy is limited due to concerns about fetal toxicity and teratogenicity, and new therapeutic avenues are being sought in alternative physiological pathways. Historically, generation of the vasodilator nitric oxide was believed to be solely from L-arginine by means of nitric oxide synthase enzymes. Recently, a novel pathway for the reduction of dietary inorganic nitrate to nitrite by the bacteria in the oral cavity and subsequently to vasodilatory nitric oxide within the body has been uncovered. Dietary nitrate is abundant in green leafy vegetables, including beetroot and spinach, and reduction of exogenous nitrate to nitrite by oral bacteria can increase nitric oxide in the vasculature, lessening hypertension. Supplements rich in nitrate may be an attractive choice for treatment due to fewer side effects than drugs that are currently used to treat hypertensive pregnancy disorders. Additionally, manipulation of the composition of the oral microbiota using pro- and prebiotics in tandem with additional dietary interventions to promote cardiovascular health during gestation may offer a safe and effective means of treating hypertensive pregnancy disorders including gestational hypertension and pre-eclampsia. The use of dietary inorganic nitrate as a supplement during pregnancy requires further exploration and large scale studies before it may be considered as part of a treatment regime. The aim of this article is to review the current evidence that oral microbiota plays a role in hypertensive pregnancies and whether it could be manipulated to improve patient outcomes.