Taekwondo is a complex martial art that requires speed, balance, agility, and endurance. This study aims to examine the effects of nitrate and L-arginine supplementation on acute aerobic and anaerobic performance, balance, agility, and recovery in elite taekwondo athletes.

This study was conducted as a double-blind, randomized, crossover study with the participation of 15 experienced taekwondo athletes aged 19.06 ± 0.96 years and 8.93 ± 1.27 years of training experience. Participants visited the laboratory a total of nine times, including a practice session and anthropometric measurements. These visits consisted of eight experimental sessions conducted at 72-hour intervals. The experimental sessions were conducted with nitrate, L-arginine, and a combination of both supplements (NIT*L-ARG) and placebo. Nitrate supplementation was provided by homogenizing fresh spinach (837.40 mg/kg), while L-ARG was given as a single dose of 6 g in powder form three hours before exercise.

NIT*L-ARG supplementation significantly improved the anaerobic performance of athletes in Wingate peak power and peak power (w/kg) compared to placebo and in mean power compared to NIT, L-ARG, and PLA. In addition, NIT*L-ARG supplementation significantly improved blood lactate levels and agility performance immediately after Wingate and Shuttle run tests.

The combined intake of NIT*L-ARG was found to be effective in improving aerobic, anaerobic, and agility performances as well as fatigue levels of athletes. It was determined that taking NIT and L-ARG supplements alone contributed to the improvement of improving athletes' performance in Wingate mean power values and subsequent fatigue level compared to PLA.

Homeostasis is the self-regulating processes in cells and organisms designed to maintain stability of the internal environment while adjusting to external changes. To achieve this dynamic stability, internal conditions oscillate within tightly regulated physiological tolerance limits. In mammals, maintaining nitric oxide (NO) availability appears crucial to sustain relatively constant blood flow into all organs and tissues. We hypothesize that NO homeostasis is one of the most important vital processes for warm-blooded animals. It is impossible to conserve the stability of most other vital substances, such as O2, CO2, blood sugar, pH, and temperature, to name just few, without well-functioning tissue perfusion. NO in mammals is generated either from L-arginine by nitric oxide synthases (NOSs) or by the reduction of nitrate (NO3-) to nitrite (NO2-) and NO by several proteins. Here we first discuss the organization of these two NO metabolic pathways, emphasizing that both pathways "cross" and "funnel" unused NO into the overall nitrate-nitrite-NO pathway. This pathway is cyclic, which gives nitrate a unique place in metabolism and predisposes it as a reservoir for NO. Then, we discuss the role of NO homeostasis that, by maintaining organ and tissue perfusion, supports and preserves constancy of other blood-delivered substances. This "governing" role of NO makes even clearer that the existence of NO storage and precursor molecules is necessary, to avoid NO shortages in cases of the precursor's or storage molecule's temporary unavailability, to ensure uninterrupted tissue access to NO. We propose that the skeletomuscular system and skin act as nitrate reservoirs assuring NO bioavailability at various external and internal conditions.

High-altitude environments present unique abiotic stresses, yet their impact on the growth, nutritional quality, and rhizospheric interactions of E. sativa remains underexplored. Here, we investigate the altitudinal variations in growth dynamics, nutritional composition, and rhizospheric free-living N2-fixing bacteria (NFBs) of E. sativa (Arugula) grown at higher (3,524 m, Leh-Ladakh) and lower (321 m, Chandigarh) altitudes. Results revealed significant physiological adaptations to high-altitude conditions, with increased concentrations of magnesium (748.84 ± 4.06 mg/100 g), iron (189.83 ± 2.16 mg/100 g), and manganese (8.48 ± 0.27 mg/100 g), while potassium (3,400.83 ± 3.82 mg/100 g), sodium (175.83 ± 1.44 mg/100 g), and copper (1.69 ± 0.01 mg/100 g) were higher at lower-altitude. Zinc content remained unchanged. Notably, dietary nitrate was higher (155.67 ± 22.12 mg/100 g) at high-altitudes. Rhizospheric NFBs were isolated and functionally characterized for N2-fixation efficacy along with various plant growth-promoting (PGP) attributes; viz., production of ammonia, siderophores, HCN, IAA and phosphate solubilization. Field inoculation with selected strains significantly enhanced nitrogen content and plant growth. Soil chemical analysis further revealed significant differences between the altitudes. A total of twenty-seven NFBs belonging to Actinobacteria (77%), Proteobacteria (11%), Firmicutes(8%), and Bacteroidetes(4%) were isolated, with Streptomyces being the predominant genus, exhibiting distinct species at different altitudes. Remarkably, high-altitude strains showed significantly higher N2-fixing efficiencies (88.15 ± 17.41 µgN mL-1) than lower-altitude (65.7 ± 14.36 µgN mL-1) along with superior PGP traits. Overall, these findings suggest that E. sativa, enriched in key nutrients at high-altitudes, could be a valuable functional food crop, addressing the dietary needs of high-altitude populations. Furthermore, the rhizospheric NFBs identified in this study may be potentially beneficial for the development of novel bio-fertilizers, promoting eco-friendly agricultural practices through improved N2-fixation. Further field trials are recommended to validate their potential for sustainable crop production.

Water polo (WP) is a high-intensity team sport that requires a combination of physical endurance, muscular strength, speed, and specific technical skills. Due to the demanding and prolonged nature of this sport, adequate and balanced nutrition plays a fundamental role in athletes' performance, recovery, and overall health maintenance.

We aimed to compile all available information on the importance of ergonutrition and supplementation in the recovery of WP players. This will help in understanding this sport's specific challenges and requirements, enabling players and coaches to design more effective recovery plans to optimize performance, achieve goals, and successfully cope with intense training and competition.

English-language publications were searched in databases such as Web of Science, Scopus, SciELO Citation Index, Medline (PubMed), KCI Korean Journal Database, and Current Contents Connect using a series of keywords such as WP, nutrition, recovery, and ergogenic aids individually or in combination.

In the field of ergonutritional recovery in WP, certain supplements such as whey protein, beta-alanine, L-arginine, spirulina, and copper can be beneficial for improving performance and recovery. In some cases, WP athletes may consider using ergogenic supplements to further improve their performance and recovery process. However, it is important to bear in mind that any supplement should be carefully evaluated under the supervision of a health professional or a sports nutritionist, as some supplements may present side effects or unwanted interactions.

Adequate ergogenic nutrition adapted to the needs of WP players is essential not only to optimize their athletic performance but also to ensure effective recovery and maintain their long-term health and general well-being. The application of these strategies should be evidence-based and tailored to the individual needs of the players and the specific demands of the sport. Future experimental research that can confirm our results is essential.

This narrative review provides an analysis of the role of nitric oxide (NO) and its precursors, particularly L-arginine, in vascular regulation and health, with an emphasis on findings from our experimental research in animal models. NO serves as a critical mediator of vascular function, contributing to vasodilation, the regulation of blood flow, and the prevention of thrombosis. As a primary precursor of NO, L-arginine is essential for maintaining endothelial integrity, modulating mitochondrial function, and reducing oxidative damage. This review synthesises the data and contextualises these findings within the physiological challenges faced by blood donors, such as repeated blood donation and associated oxidative stress. It examines the effects of L-arginine supplementation on mitochondrial respiration, lipid peroxidation, and microsomal oxidation in different conditions, including differences in age, gender, and dietary interventions. The mechanisms by which L-arginine enhances NO production, improves vascular elasticity, and alleviates endothelial dysfunction caused by reduced NO bioavailability are also investigated. By integrating experimental findings with insights from the existing literature, this review provides a perspective on the potential of L-arginine supplementation to address the specific physiological needs of blood donors. It highlights the importance of personalised nutritional approaches in enhancing donor recovery and vascular resilience. In addition, this review assesses the wider implications of L-arginine supplementation in mitigating oxidative stress and preserving vascular function. The interplay between NO bioavailability, dietary factors, and physiological adaptation in blood donors is highlighted, along with the identification of current knowledge gaps and recommendations for future research. By presenting both original experimental evidence and a critical synthesis of the literature, this article highlights the therapeutic potential of NO precursors, particularly L-arginine, in promoting vascular health in the context of blood donation.

Green leafy vegetables (GLV) are known for their cardiovascular health benefits. However, the effects of their serving size on delaying carbohydrate and lipid digestion remain unclear. This study investigated the impact of varying MyPlate-recommended GLV serving sizes on the digestibility of carbohydrates and lipids and antioxidant activity during in vitro gastrointestinal digestion. Eight GLV including Asteraceae (cos, green oak, red oak, loose-leaf) and Brassicaceae (cabbage, cauliflower, broccoli, Chinese cabbage) vegetables were incorporated into mixed meals at 0.5, 1.0, and 1.5 times the MyPlate recommendation. The results showed that the total phenolic content (TPC) ranged from 5.77 to 9.46 mg GAE/g extract. Nitrate accumulation exhibited a higher content in Asteraceae (590.90-1155.04 mg NO3-NE/g extract) than in Brassicaceae families (244.96-726.20 mg NO3-NE/g extract). Incorporating ≥ 1 serving of all GLV significantly decreased rapidly and slowly digestible starch fractions, while undigestible starch significantly increased, resulting in delaying glucose release. Antioxidant activity was significantly enhanced with ≥ 1 serving and free fatty acid concentrations decreased with higher vegetable servings. Post-digestion nitrate concentrations ranged from 127.3 to 188.5 µg NO3-N/mL, positively correlating with GLV serving size. These effects were dose-dependent and varied across species. These findings suggest that incorporating GLV at or above the MyPlate recommendation may have protective effects on cardiovascular health.

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.

This study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration.

In this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series.

Seventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m2, FEV1, 0.79 (0.67-1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels.

Acute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect.

Exogenous nitrate ingestion can improve exercise performance. This study investigated whether an isotonic beetroot drink could improve jump and sprint performance in active individuals. Twenty-three physically active participants (17 males, 6 females) (mean ± SD; age: 26 ± 4 years; body mass index: 22.4 ± 1.9 kg/m2) completed a double-blind, randomized, cross-over study where they consumed 570mL of either beetroot juice drink (BR) or isotonic beetroot juice drink (ISO-BR) three hours before performing countermovement (CMJ) and standing broad jump (SBJ) tests and a 30-second all-out sprint on a cycle ergometer. Both drinks contained equal nitrate (12.9 mmol) and carbohydrate (6.1g per 100mL) content but differed in osmolality (BR: 420 mOsm/kg vs. ISO-BR: 315 mOsm/kg). Salivary total nitrate and nitrite concentrations (NOx) 3 hours post-ingestion were significantly higher after consuming ISO-BR than BR. ISO-BR significantly improved peak power output compared to BR by 3.9% (ISO-BR: 11.4 ± 2.5 W/kg vs. BR: 11.0 ± 2.3 W/kg, p = .04) but not time to peak power (ISO-BR: 2.8 ± 1.7 s vs. BR: 2.9 ± 1.6 s, p = .62) or mean power output (ISO-BR: 7.3 ± 1.5 W/kg vs. BR: 7.3 ± 1.5 W/kg, p = .37). There were no significant differences in CMJ or SBJ between trials (p > .05). Sensory evaluation indicated that ISO-BR was preferred by 91% (n = 21) of participants compared with BR (average score; ISO-BR: 5.52 vs. BR: 3.52, p < .05). An ISO-BR drink improved peak power output during sprint cycling but not jump performance compared with BR alone, potentially via increased NOx.

Metabolic syndrome (MetS) prevalence has increased globally.The evidence shows thatdiet and gut microbial metabolites includingtrimethylamine N-oxide (TMAO) and kynurenine (KYN) play an important role in developing MetS. However, there is a lack of evidence on associations between between diet and these metabolites. This study aimed to investigate the interaction between dietary nitrate/nitrite and gut microbial metabolites (TMAO, KYN) on MetS and its components.

This cross-sectional study included 250 adults aged 20-50 years. Dietary intake was assessed using food frequency questionnaires (FFQ), and serum TMAO and KYN levels were measured. MetS was defined usingthe National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria.

The ATPIII index revealed an 11% prevalence of metabolic syndrome among the study participants. After adjusting for confounders, significant positive interactions were found: High animal-source nitrate intake and high TMAO levels with elevated triglycerides (TG) (p interaction = 0.07) and abdominal obesity (p interaction = 0.08). High animal-source nitrate intake and high KYN levels with increased TG (p interaction = 0.01) and decreased high-density lipoprotein cholesterol (HDL) (p interaction = 0.01).Individuals with high animal-source nitrite intake and high TMAO levels showed increased risk of hypertriglyceridemia (OR: 1.57, 95%CI: 0.35-2.87, p = 0.05), hypertension (OR: 1.53, 95%CI: 0.33-2.58, p = 0.06), and lower HDL (OR: 1.96, 95%CI: 0.42-2.03, p = 0.04). Similarly, high animal-source nitrite intake with high KYN levels showed lower HDL (OR: 2.44, 95%CI: 1.92-3.89, p = 0.07) and increased risk of hypertension (OR: 2.17,95%CI: 1.69-3.40, p = 0.05). Conversely, Negative interactions were found between high plant-source nitrate/nitrite intake with high KYN and TMAO levels on MetS and some components.

There is an interaction between dietary nitrate/nitrite source (animal vs. plant) and gut microbial metabolites (TMAO and KYN) on the risk of of MetS and its components. These findings highlight the importance of considering diet, gut microbiome metabolites, and their interactions in MetS risk assessment.

Ageing is a natural ontogenetic phenomenon that entails a decrease in the adaptive capacity of the organism, as a result of which the body becomes less adaptable to stressful conditions. Nitrate and nitrite enter the body from exogenous sources and from nitrification of ammonia nitrogen by intestinal microorganisms. This review considers the mechanisms of action of l-arginine, a known inducer of nitric oxide (NO) biosynthesis, and nitrates as supplements in the processes of ageing and aggravated stress states, in which mechanisms of individual physiological reactivity play an important role. This approach can be used as an element of individual therapy or prevention of premature ageing processes depending on the different levels of initial reactivity of the functional systems. A search was performed of the PubMed, Scopus, and Google Scholar databases (n = 181 articles) and the author's own research (n = 4) up to May 5, 2023. The review presents analyses of data on targeted treatment of NO generation by supplementation with l-arginine or nitrates, which is a promising means for prevention of hypoxic conditions frequently accompanying pathological processes in an ageing organism. The review clarifies the role of the individual state of physiological reactivity, using the example of individuals with a high predominance of cholinergic regulatory mechanisms who already have a significant reserve of adaptive capacity. In studies of the predominance of adrenergic influences, a poorly trained organism as well as an elderly organism correspond to low resistance, which is an additional factor of damage at increased energy expenditure.

It is suggested that the role of NO synthesis from supplementation of dietary nitrates and nitrites increases with age rather than from oxygen-dependent biosynthetic reactions from l-arginine supplementation.

Interest 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.

Cardiovascular diseases (CVDs) are often associated with impaired nitric oxide (NO) bioavailability, a critical pathophysiological alteration in CVDs and an important target for therapeutic interventions. Recent studies have revealed the potential of inorganic nitrite and nitrate as sources of NO, offering promising alternatives for managing various cardiovascular conditions. It is now becoming clear that taking advantage of enzymatic pathways involved in nitrite reduction to NO is very relevant in new therapeutics. However, recent studies have shown that nitrite may be bioactivated in the acidic gastric environment, where nitrite generates NO and a variety of S-nitrosating compounds that result in increased circulating S-nitrosothiol concentrations and S-nitrosation of tissue pharmacological targets. Moreover, transnitrosation reactions may further nitrosate other targets, resulting in improved cardiovascular function in patients with CVDs. In this review, we comprehensively address the mechanisms and relevant effects of nitrate and nitrite-stimulated gastric S-nitrosothiol formation that may promote S-nitrosation of pharmacological targets in various CVDs. Recently identified interfering factors that may inhibit these mechanisms and prevent the beneficial responses to nitrate and nitrite therapy were also taken into consideration.

Nitric oxide (NO) is a vasodilator gas that plays a critical role in mitochondrial respiration and skeletal muscle function. NO is endogenously generated by NO synthases: neuronal NO synthase (nNOS), endothelial NO synthase (eNOS), or inducible NO synthase (iNOS). NO in skeletal muscle is partly generated by nNOS, and nNOS deficiency can contribute to muscular dystrophic diseases. However, we and others discovered an alternative nitrate/nitrite reductive pathway for NO generation: nitrate to nitrite to NO. We hypothesized that nitrate supplementation would increase nitrate accumulation in skeletal muscle and promote a nitrate/nitrite reductive pathway for NO production to compensate for the loss of nNOS in skeletal muscle.

Wild-type (WT) and genetic nNOS knockout (nNOS-/-) mice were fed normal chow (386.9 nmol/g nitrate) and subjected to three treatments: high-nitrate water (1 g/L sodium nitrate for 7 days), low-nitrate diet (46.8 nmol/g nitrate for 7 days), and low-nitrate diet followed by high-nitrate water for 7 days each.

High-nitrate water supplementation exhibited a greater and more significant increase in nitrate levels in skeletal muscle and blood in nNOS-/- mice than in WT mice. A low-nitrate diet decreased blood nitrate and nitrite levels in both WT and nNOS-/- mice. WT and nNOS-/- mice, treated with low-nitrate diet, followed by high-nitrate water supplementation, showed a significant increase in nitrate levels in skeletal muscle and blood, analogous to the increases observed in nNOS-/- mice supplemented with high-nitrate water. In skeletal muscle of nNOS-/- mice on high-nitrate water supplementation, on low-nitrate diet, and in low-high nitrate treatment, the loss of nNOS resulted in a corresponding increase in the expression of nitrate/nitrite reductive pathway-associated nitrate transporters [sialin and chloride channel 1 (CLC1)] and nitrate/nitrite reductase [xanthine oxidoreductase (XOR)] but did not show a compensatory increase in iNOS or eNOS protein and eNOS activation activity [p-eNOS (Ser1177)].

These findings suggest that a greater increase in nitrate levels in skeletal muscle of nNOS-/- mice on nitrate supplementation results from reductive processes to increase NO production with the loss of nNOS in skeletal muscle.

Background and objectives Dietary nitrate (NO3) plays an important role in human physiological processes. In the past, inorganic NO3 was viewed negatively due to its link with carcinogenic effects, notably nitrosamine formation in the stomach; yet, current perspectives acknowledge NO3 as a potentially beneficial dietary element. Nutrition professionals (NPs) are crucial in promoting NO3 awareness in health and academic settings. The study aimed to evaluate the knowledge of NPs in Jeddah, Saudi Arabia, regarding the biological roles of dietary NO3, taking into consideration their qualifications and years of experience. Methods A cross-sectional study was conducted among NPs who had graduated from clinical nutrition programs or were employed in clinical or academic settings. A validated 12-item online questionnaire was used to assess dietary NO3 knowledge across five areas: health effects, dietary sources, recommendations, biomarkers of intake, and metabolism. The nitrate knowledge index (NKI) score was used to evaluate responses. Results Eighty-nine female NPs out of 144 completed the questionnaire. Most were ≤30 years old (75.4%) and had an undergraduate degree in clinical nutrition (70.8%), but 37 of them had ≤3 years of experience (62.7%). Overall, poor knowledge scores were observed among NPs, with a median (25th and 75th percentile) score of 10 (6, 13) out of 23. The majority (64%) perceived NO3 to be beneficial. However, most of the participants did not know its benefits in lowering blood pressure (BP) (68.5%) and were unsure about the effects of nitrate on cognitive function (60.7%) or kidney function (57.3%). Almost half of the NPs were unaware of NO3 sources and unsure about the mechanisms of the conversion of NO3 into nitrogen dioxide (NO2) in the mouth (48.3%). Overall, knowledge of factors that affect NO3 content in food was good. No significant differences were observed in the median NKI scores among the participants based on their level of education or years of experience. Conclusion This study suggests NPs lack knowledge about dietary NO3. To address this, educational programs should be developed and implemented in clinical and academic settings.

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

Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo.

This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed.

Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured.

Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.

Nitric oxide (NO) is an inorganic radical produced by both the non-enzymatic nitrate (NO3-)-nitrite (NO2-)-NO pathway and enzymatic reactions catalyzed by nitric oxide synthase (NOS). Also, as nitrate and nitrite from dietary and other endogenous sources can be reduced back to nitric oxide in vivo, the endogenous NO level can be increased through the consumption of nitrate-rich vegetables. Ingestion of dietary NO3- has beneficial effects which have been attributed to a subsequent increase in NO: a signaling molecule that may regulate various systems, including the cardiovascular system. A diet rich in NO3- from green leafy and root vegetables has cardioprotective effects, with beetroot products being particularly good sources of NO3-. For example, various studies have demonstrated a significant increase in nitrite levels (regarded as markers of NO) in plasma after the intake of beetroot juice. The present review describes the current literature concerning the role of nitrate-rich vegetables (especially beetroot products) in the prophylaxis and treatment of cardiovascular diseases (CVDs). This review is based on studies identified in electronic databases, including PubMed, ScienceDirect, Web of Knowledge, Sci Finder, Web of Science, and SCOPUS.

Dietary nitrates (NO3-) are naturally occurring compounds in various vegetables, especially beetroot, which is mainly supplemented in the form of BRJ. Dietary nitrates (NO3-) play a crucial function in human physiology. On consumption, nitrates (NO3-) undergo a conversion process, producing nitric oxide (NO) via a complex metabolic pathway. Nitric oxide (NO) is associated with many physiological processes, entailing immune modulation, neurotransmission, and vasodilation, enabling blood vessel dilation and relaxation, which boosts blood flow and oxygen delivery to tissues, positively influencing cardiovascular health, exercise performance, and cognitive function. There are various analytical processes to determine the level of nitrate (NO3-) present in dietary sources. The impact of dietary nitrates (NO3-) can differ among individuals. Thus, the review revisits the dietary source of nitrates (NO3-), its metabolism, absorption, excretion, analytical techniques to assess nitrates (NO3-) content in various dietary sources, and discusses health effects.

Beetroot juice is a popular natural food supplement commonly consumed for its health and ergogenic benefits. It contains an abundance of phytochemical compounds, which have been shown to enhance sports endurance and recovery. Among them, nitrate is well-studied and known for improving performance during exercise. On the other hand, betalains, the bioactive pigment, have shown various biological activities including antioxidant, anti-inflammatory, and anti-hypertensive, which may improve exercise performance and post-exercise recovery. Additionally, free radical scavenging activities of betalains could increase nitric oxide availability in the blood, thereby improving blood flow and oxygen supply during strenuous exercise. This review article provides a critical discussion of the non-pathological conditions induced by prolonged or strenuous exercise and betalains' potential in reducing such conditions including muscle damage, inflammation, and fatigue. Additionally, the real-time application of betalains as an ergogenic compound in competitive athletes has been discussed. Finally, future directions and conclusions on the potential of betalains as a natural ergogenic aid in sport endurance are outlined.

Betalains in beetroot are the major water-soluble nitrogen-containing pigment possessing high antioxidant, anti-inflammatory, and anti-fatigue activities. Betalain supplementation could alleviate exercise-induced oxidative stress, inflammation, and fatigue in competitive athletes. Betalains have the potential to become a natural ergogenic aid or nutraceutical compound for sports people during exercise and competitive performance.

Hypertension in pregnancy is prevalent, affecting around 10% of pregnancies worldwide, and significantly increases the risk of adverse outcomes for both mothers and their babies. Current treatment strategies for pregnant women with hypertension are limited, and new approaches for the management of hypertension in pregnancy are urgently needed. Substantial evidence from non-pregnant subjects has demonstrated the potential for dietary nitrate supplementation to increase nitric oxide (NO) bioavailability and lower blood pressure, following bioactivation via the non-canonical NO pathway. Emerging data suggest this approach may also be of benefit in pregnant women, although studies are limited. This review aims to summarise the current evidence from preclinical and clinical studies of nitrate supplementation in pregnancy, drawing on data from non-pregnant populations where appropriate and highlighting key gaps in knowledge that remain to be addressed in future trials.

Menopause is associated with reduced nitric oxide bioavailability and vascular function. Although exercise is known to improve vascular function, this is blunted in estrogen-deficient females post-menopause (PM). Here, we examined the effects of acute exercise at differing intensities with and without inorganic nitrate (NO3-) supplementation on vascular function in females PM. Participants were tested in a double-blinded, block-randomized design, consuming ∼13 mmol NO3- in the form of beetroot juice (BRJ; n = 12) or placebo (PL; n = 12) for 2 days before experimental visits and 2 h before testing. Visits consisted of vascular health measures before (time point 0) and every 30 min after (time points 60, 90, 120, 150, and 180) calorically matched high-intensity exercise (HIE), moderate-intensity exercise (MIE), and a nonexercise control (CON). Blood was sampled at rest and 5-min postexercise for NO3-, NO2-, and ET-1. BRJ increased N-oxides and decreased ET-1 compared with PL, findings which were unchanged after experimental conditions (P < 0.05). BRJ improved peak Δflow-mediated dilation (FMD) compared with PL (P < 0.05), defined as the largest ΔFMD for each individual participant across all time points. FMD across time revealed an improvement (P = 0.05) in FMD between BRJ + HIE versus BRJ + CON, while BRJ + MIE had medium effects compared with BRJ + CON. In conclusion, NO3- supplementation combined with HIE improved FMD in postmenopausal females. NO3- supplementation combined with MIE may offer an alternative to those unwilling to perform HIE. Future studies should test whether long-term exercise training at high intensities with NO3- supplementation can enhance vascular health in females PM.NEW & NOTEWORTHY This study compared exercise-induced changes in flow-mediated dilation after acute moderate- and high-intensity exercise in females postmenopause supplementing either inorganic nitrate (beetroot juice) or placebo. BRJ improved peak ΔFMD postexercise, and BRJ + HIE increased FMD measured as FMD over time. Neither PL + MIE nor PL + HIE improved FMD. These findings suggest that inorganic nitrate supplementation combined with high-intensity exercise may benefit vascular health in females PM.

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.

Nitric oxide (NO) has been implicated in the pathology of malaria. This systematic review and meta-analysis describe the association between NO levels and malaria. Embase, Ovid, PubMed, Scopus, and Google Scholar were searched to identify studies evaluating NO levels in malaria patients and uninfected controls. Meta-regression and subgroup analyses were conducted to discern differences in NO levels between the groups. Of the 4517 records identified, 21 studies were included in the systematic review and meta-analysis. The findings illustrated significant disparities in NO levels based on geographic location and study time frames. Despite the fluctuations, such as higher NO levels in adults compared to children, no significant differences in mean NO levels between patients and uninfected controls (p = 0.25, Hedge's g: 0.35, 95% confidence interval (CI): -0.25-0.96, I2: 97.39%) or between severe and non-severe malaria cases (p = 0.09, Hedge's g: 0.71, 95% CI: -0.11-1.54, I2: 96.07%) were detected. The systematic review and meta-analysis highlighted inconsistencies in NO levels in malaria patients. Given the high heterogeneity of the results, further studies using standardized metrics for NO measurements and focusing on biochemical pathways dictating NO responses in malaria are imperative to understand the association between NO and malaria.

Dietary nitrate (NO3-) supplementation can enhance nitric oxide (NO) bioavailability and lower blood pressure (BP) in humans. The nitrite concentration ([NO2-]) in the plasma is the most commonly used biomarker of increased NO availability. However, it is unknown to what extent changes in other NO congeners, such as S-nitrosothiols (RSNOs), and in other blood components, such as red blood cells (RBC), also contribute to the BP lowering effects of dietary NO3-. We investigated the correlations between changes in NO biomarkers in different blood compartments and changes in BP variables following acute NO3- ingestion. Resting BP was measured and blood samples were collected at baseline, and at 1, 2, 3, 4 and 24 h following acute beetroot juice (∼12.8 mmol NO3-, ∼11 mg NO3-/kg) ingestion in 20 healthy volunteers. Spearman rank correlation coefficients were determined between the peak individual increases in NO biomarkers (NO3-, NO2-, RSNOs) in plasma, RBC and whole blood, and corresponding decreases in resting BP variables. No significant correlation was observed between increased plasma [NO2-] and reduced BP, but increased RBC [NO2-] was correlated with decreased systolic BP (rs = -0.50, P = 0.03). Notably, increased RBC [RSNOs] was significantly correlated with decreases in systolic (rs = -0.68, P = 0.001), diastolic (rs = -0.59, P = 0.008) and mean arterial pressure (rs = -0.64, P = 0.003). Fisher's z transformation indicated no difference in the strength of the correlations between increases in RBC [NO2-] or [RSNOs] and decreased systolic blood pressure. In conclusion, increased RBC [RSNOs] may be an important mediator of the reduction in resting BP observed following dietary NO3- supplementation.

In both developed and developing countries, non-alcoholic fatty liver disease (NAFLD) has lately risen to the top of the list of chronic liver illnesses. Although there is no permanent cure, early management, diagnosis, and treatment might lessen its effects. The purpose of conducting the current study is to compare the effects of beetroot juice and the Mediterranean diet on the lipid profile, level of liver enzymes, and liver sonography in patients with NAFLD.

In this randomized controlled trial, 180 people with a mean age of (45.19 ± 14.94) years participated. Participants ranged in age from 19 to 73. The mean weight before intervention was (82.46 ± 5.97) kg, while the mean weight after intervention was roughly (77.88 ± 6.26) kg. The trial lasted for 12 weeks. The participants were split into four groups: control, a Mediterranean diet with beet juice (BJ + MeD), Mediterranean diet alone (MeD), and beetroot juice (BJ). The Mediterranean diet included fruits, vegetables, fish, poultry, and other lean meats (without skin), sources of omega-3 fatty acids, nuts, and legumes. Beetroot juice had 250 mg of beetroot. Data analysis was done using SPSS software (version 26.0). p < 0.05 is the statistical significance level.

Following the intervention, Serum Bilirubin, alkaline phosphatase (ALP), alanine transaminase (ALT), serum cholesterol (CHOL), triglyceride (TG), and low-density lipoprotein (LDL) levels were significantly decreased in the BJ + MeD, BJ, and MeD groups (p = 0.001). Also, high-density lipoprotein (HDL) significantly increased in the BJ + MeD, BJ, and MeD groups (p = 0.001), while decreasing in the Control group (p = 0.001).

The research findings indicate a significant reduction in hepatic steatosis among the groups receiving beetroot juice (BJ) and beetroot juice combined with the Mediterranean diet (BJ + MeD). This suggests that beetroot juice holds potential as an effective treatment for non-alcoholic fatty liver disease (NAFLD) in adults. Furthermore, the combination of beetroot juice with the Mediterranean diet showed enhanced efficacy in addressing NAFLD.Clinical trial registration: ClinicalTrials.gov, identifier NCT05909631.

The purpose of the study was to evaluate and compare the levels of salivary Interleukin-6 (IL-6) before and after the placement of dental implants in patients who are supplemented with nitric oxide (NO).

The study comprised 34 patients, divided into control and study groups (17 in each group). The control group was given a placebo and in the study group, nitric oxide supplement was prescribed, whereas the control group received a placebo. Saliva samples were taken before placement of dental implants, first and third day after the implant placement. The levels of salivary IL-6 were assessed using an enzyme-linked immunosorbent assay test.

Statistical analysis showed a significant P value (<0.05) with respect to IL-6 levels on first and third days after placement of dental implants. Salivary IL-6 levels in the study group declined significantly. On day three, the IL-6 values for the control and study groups were 0.0639 and 0.0443, respectively. Within the groups, it was observed that there was a significant decrease in IL-6 values from day one to day three.

The levels of salivary IL-6 reduced from day one to day three more significantly and consistently in patients prescribed with NO supplements post-dental implant placement, suggesting better resolution of inflammation.

Pathophysiological conditions such as endothelial dysfunction and arterial stiffness, characterized by low nitric oxide bioavailability, deficient endothelium-dependent vasodilation and heart effort, predispose individuals to atherosclerotic lesions and cardiac events. Nitrate (NO₃^-), L-arginine, L-citrulline and potassium (K⁺) can mitigate arterial dysfunction and stiffness by intensifying NO bioavailability. Dietary compounds such as L-arginine, L-citrulline, NO₃^- and K⁺ exert vasoactive effects as demonstrated in clinical interventions by noninvasive flow-mediated vasodilation (FMD) and pulse-wave velocity (PWV) prognostic techniques. Daily L-arginine intakes ranging from 4.5 to 21 g lead to increased FMD and reduced PWV responses. Isolated L-citrulline intake of at least 5.6 g has a better effect compared to watermelon extract, which is only effective on endothelial function when supplemented for longer than 6 weeks and contains at least 6 g of L-citrulline. NO₃^- supplementation employing beetroot at doses greater than 370 mg promotes hemodynamic effects through the NO₃^--NO2-/NO pathway, a well-documented effect. A potassium intake of 1.5 g/day can restore endothelial function and arterial mobility, where decreased vascular tone takes place via ATPase pump/hyperpolarization and natriuresis, leading to muscle relaxation and NO release. These dietary interventions, alone or synergically, can ameliorate endothelial dysfunction and should be considered as adjuvant therapies in cardiovascular diseases.

Dietary modification is a cornerstone of cardiovascular disease (CVD) prevention. A Mediterranean diet has been associated with a lower risk of CVD but no systematic reviews have evaluated this relationship specifically in women.

To determine the association between higher versus lower adherence to a Mediterranean diet and incident CVD and total mortality in women.

A systematic search of Medline, Embase, CINAHL, Scopus, and Web of Science (2003-21) was performed. Randomised controlled trials and prospective cohort studies with participants without previous CVD were included. Studies were eligible if they reported a Mediterranean diet score and comprised either all female participants or stratified outcomes by sex. The primary outcome was CVD and/or total mortality. A random effects meta-analysis was conducted to calculate pooled hazard ratios (HRs) and confidence intervals (CIs).

Sixteen prospective cohort studies were included in the meta-analysis (n=7 22 495 female participants). In women, higher adherence to a Mediterranean diet was associated with a lower CVD incidence (HR 0.76, 95% CI 0.72 to 0.81; I²=39%, p test for heterogeneity=0.07), total mortality (HR 0.77, 95% CI 0.74 to 0.80; I²=21%, p test for heterogeneity=0.28), and coronary heart disease (HR 0.75, 95% CI 0.65 to 0.87; I²=21%, p test for heterogeneity=0.28). Stroke incidence was lower in women with higher Mediterranean diet adherence (HR 0.87, 95% CI 0.76 to 1.01; I²=0%, p test for heterogeneity=0.89), but this result was not statistically significant.

This study supports a beneficial effect of the Mediterranean diet on primary prevention of CVD and death in women, and is an important step in enabling sex specific guidelines.

Several studies have shown inorganic nitrate/nitrite to reduce blood pressure in both healthy subjects and hypertensive patients. An effect presumably caused through bioconversion to nitric oxide. However, studies on inorganic nitrate/nitrite have shown inconsistent results on renal functions such as GFR and sodium excretion. The current study investigated whether orally administered nitrate would decrease blood pressure and increase GFR and urinary sodium excretion.

In a randomized, placebo-controlled, double-blinded, crossover study, 18 healthy subjects received a daily dose of 24 mmol potassium nitrate and placebo (potassium chloride) during 4 days in a randomized order. Subjects also ingested a standardized diet and completed a 24-h urine collection. GFR was determined by the constant infusion technique and during GFR measurement, brachial blood pressure (BP) and central blood pressure (cBP), heart rate, and arterial stiffness were measured every half hour using the Mobil-O-Graph®. Blood samples was analyzed for nitrate, nitrite, cGMP, vasoactive hormones and electrolytes. Urine was analyzed for nitrate, nitrite, cGMP, electrolytes, ENaC_γ, NCC, CrCl, C_H2O and UO.

No differences in GFR, blood pressure or sodium excretion were found between the treatments with potassium nitrate and placebo. However, both nitrate and nitrite levels in plasma and urine were significantly increased by potassium nitrate intake and the 24-h urinary excretion of sodium and potassium were stable, showing adherence to the standardized diet and the study medication.

We found no decrease in blood pressure or increase in GFR and sodium excretion of 24 mmol potassium nitrate capsules as compared to placebo after 4 days of treatment. Healthy subjects may be able to compensate the effects of nitrate supplementation during steady state conditions. Future research should focus on long-term studies on the difference in response between healthy subjects and patients with cardiac or renal disease.

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 nitrates may play a role in mediating several key physiological processes impacting health and/or exercise performance. However, current methods for assessing dietary nitrate (NO3 - ) consumption are inadequate. The present study aimed to examine the dietary nitrate intake in a sample of 50 healthy adults, as well as test the validity of a purposefully developed food frequency questionnaire (FFQ).

Dietary nitrate intake was estimated over a week using (i) three 24-h dietary recalls; (ii) a short-term (7-day) FFQ; and (iii) a biomarker (urinary nitrate), in conjunction with a nitrate reference database.

Daily dietary nitrate intake estimates were 130.94 mg (average of three 24-h recalls) and 180.62 mg (FFQ). The mean urinary NO3 - excretion was 1974.79 µmol day-1 (or 917.9 µmol L-1 ). Despite the difference between the two dietary assessment methods, there was a moderate positive correlation (r = 0.736, ρ < 0.001) between the two tools. There was also a positive correlation between urinary NO3 - and 24-h recall data (r = 0.632, ρ < 0.001), as well as between urinary NO3 - and FFQ (r = 0.579, ρ < 0.001).

The ability to accurately estimate nitrate intakes depends on having suitable reference methods to estimate the concentrations of nitrate in the food supply, coupled with valid and reliable dietary assessment tools. Based on the findings from the present study, at an individual level, dietary recalls or records may be more accurate in estimating intakes of NO3 - . However, given the lower cost and time needed for administration relative to recalls, the FFQ has merit for estimating NO3 - intakes in health interventions, dietary surveys and surveillance programs.

Beetroot juice (BRJ) improves peripheral endothelial function and vascular compliance, likely due to increased nitric oxide bioavailability. It is unknown if BRJ alters cerebrovascular function and cardiovagal baroreflex control in healthy individuals.

We tested the hypotheses that BRJ consumption improves cerebral autoregulation (CA) and cardiovagal baroreflex sensitivity (cBRS) during lower-body negative pressure (LBNP).

Thirteen healthy adults (age: 26 ± 4 years; 5 women) performed oscillatory (O-LBNP) and static LBNP (S-LBNP) before (PRE) and 3 h after consuming 500 mL of BRJ (POST). Participants inhaled 3% CO2 (21% O2, 76% N2) during a 5 min baseline and throughout LBNP to attenuate reductions in end-tidal CO2 tension (PETCO2). O-LBNP was conducted at ∼0.02 Hz for six cycles (-70 mmHg), followed by a 3-min recovery before S-LBNP (-40 mmHg) for 7 min. Beat-to-beat middle cerebral artery blood velocity (MCAv) (transcranial Doppler) and blood pressure were continuously recorded. CA was assessed using transfer function analysis to calculate coherence, gain, and phase in the very-low-frequency (VLF; 0.020-0.070 Hz) and low-frequency bands (LF; 0.07-0.20 Hz). cBRS was calculated using the sequence method. Comparisons between POST vs. PRE are reported as mean ± SD.

During O-LBNP, coherence VLF was greater at POST (0.55 ± 0.06 vs. 0.46 ± 0.08; P < 0.01), but phase VLF (P = 0.17) and gain VLF (P = 0.69) were not different. Coherence LF and phase LF were not different, but gain LF was lower at POST (1.03 ± 0.20 vs. 1.12 ± 0.30 cm/s/mmHg; P = 0.05). During S-LBNP, CA was not different in the VLF or LF bands (all P > 0.10). Up-cBRS and Down-cBRS were not different during both LBNP protocols.

These preliminary data indicate that CA and cBRS during LBNP in healthy, young adults is largely unaffected by an acute bolus of BRJ.

This case-control study aimed to assess the effect of drinking water nitrate on serum nitric oxide concentration and the risk of metabolic syndrome (MetS) in the population in the Middle East. The study included 50 control and 50 thyroid disorder cases who were referred to two medical centers in 2021. In this study, serum nitric oxide concentration, drinking water nitrate, and metabolic syndrome components were measured in the two groups. The results showed there was a statistically significant difference between serum NO in the case and control groups (p-value < 0.001). There was a positive correlation between the concentration of nitrate in drinking water and serum nitric oxide in the case and control groups; however, this relationship was not significant statistically. A statistically significant difference was found between serum nitric oxide and systolic blood pressure in the cases (p-value < 0.05), but there was no significant difference between MetS and nitric oxide. Therefore, we concluded that the relationship between nitric oxide and nitrate in consuming water should be determined in thyroid patients. In addition to their water consumption, it is better to study the nitrate of foods, especially vegetables.

Exposure to low levels of nitrate in drinking water may have adverse reproductive effects. We reviewed evidence about the association between nitrate in drinking water and adverse reproductive outcomes published to November 2022. Randomized trials, cohort or case-control studies published in English that reported the relationship between nitrate intake from drinking water and the risk of perinatal outcomes were included. Random-effect models were used to pool data. Three cohort studies showed nitrate in drinking water is associated with an increased risk of preterm birth (odds ratio for 1 mg/L NO3-N increased (OR1) = 1.01, 95% CI 1.00, 1.01, I2 = 23.9%, 5,014,487 participants; comparing the highest versus the lowest nitrate exposure groups pooled OR (ORp) = 1.05, 95% CI 1.01, 1.10, I2 = 0%, 4,152,348 participants). Case-control studies showed nitrate in drinking water may be associated with the increased risk of neural tube defects OR1 = 1.06, 95% CI 1.02, 1.10; 2 studies, 2196 participants; I2 = 0%; and ORp = 1.51, 95% CI 1.12, 2.05; 3 studies, 1501 participants; I2 = 0%). The evidence for an association between nitrate in drinking water and risk of small for gestational age infants, any birth defects, or any congenital heart defects was inconsistent. Increased nitrate in drinking water may be associated with an increased risk of preterm birth and some specific congenital anomalies. These findings warrant regular review as new evidence becomes available.

Despite advances in our understanding of the pathophysiology of many cardiovascular diseases (CVDs) and expansion of available therapies, the global burden of CVD-associated morbidity and mortality remains unacceptably high. Important gaps remain in our understanding of the mechanisms of CVD and determinants of disease progression. In the past decade, much research has been conducted on the human microbiome and its potential role in modulating CVD. With the advent of high-throughput technologies and multiomics analyses, the complex and dynamic relationship between the microbiota, their 'theatre of activity' and the host is gradually being elucidated. The relationship between the gut microbiome and CVD is well established. Much less is known about the role of disruption (dysbiosis) of the oral microbiome; however, interest in the field is growing, as is the body of literature from basic science and animal and human investigations. In this Review, we examine the link between the oral microbiome and CVD, specifically coronary artery disease, stroke, peripheral artery disease, heart failure, infective endocarditis and rheumatic heart disease. We discuss the various mechanisms by which oral dysbiosis contributes to CVD pathogenesis and potential strategies for prevention and treatment.

Western-type diet with high salt and sugar, sedentary behavior, obesity, tobacco and alcoholism are important risk factors for hypertension. This review aims to highlight the role of western diet-induced oxidative stress and inflammation in the pathogenesis of hypertension and the role of various types of diets in its prevention with reference to dietary approaches to stop hypertension (DASH) diet. It seems that it is crucial to alter the western type of diet because such diets can also predispose all CVDs. Western diet-induced oxidative stress is characterized by excessive production of reactive oxygen species (ROS) with an altered oxidation-reduction (redox) state, leading to a marked increase in inflammation and vascular dysfunction. Apart from genetic and environmental factors, one important cause for differences in the prevalence of hypertension in various countries may be diet quality, deficiency in functional foods, and salt consumption. The role of the DASH diet has been established. However, there are gaps in knowledge about the role of some Indo-Mediterranean foods and Japanese foods, which have been found to decrease blood pressure (BP) by improving vascular function. The notable Indo-Mediterranean foods are pulses, porridge, spices, and millets; fruits such as guava and blackberry and vegetables, which may also decrease BPs. The Japanese diet consists of soya tofu, whole rice, in particular medical rice, vegetables and plenty of fish rich in fish oil, fish peptides and taurine that are known to decrease BPs. Epidemiological studies and randomized, controlled trials have demonstrated the role of these diets in the prevention of hypertension and metabolic diseases. Such evidence is still meager from Japan, although the prevalence of hypertension is lower (15-21%) compared to other developed countries, which may be due to the high quality of the Japanese diet. Interestingly, some foods, such as berries, guava, pumpkin seeds, carrots, soya beans, and spices, have been found to cause a decrease in BPs. Omega-3 fatty acids, fish peptide, taurine, dietary vitamin D, vitamin C, potassium, magnesium, flavonoids, nitrate and l-arginine are potential nutrients that can also decrease BPs. Larger cohort studies and controlled trials are necessary to confirm our views.

Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents.

We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events.

Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common.

Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required.

ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.

Viral infections are a continuing global burden on the human population, underscored by the ramifications of the COVID-19 pandemic. Current treatment options and supportive therapies for many viral infections are relatively limited, indicating a need for alternative therapeutic approaches. Virus-induced damage occurs through direct infection of host cells and inflammation-related changes. Severe cases of certain viral infections, including COVID-19, can lead to a hyperinflammatory response termed cytokine storm, resulting in extensive endothelial damage, thrombosis, respiratory failure, and death. Therapies targeting these complications are crucial in addition to antiviral therapies. Nitric oxide and hydrogen sulfide are two endogenous gasotransmitters that have emerged as key signaling molecules with a broad range of antiviral actions in addition to having anti-inflammatory properties and protective functions in the vasculature and respiratory system. The enhancement of endogenous nitric oxide and hydrogen sulfide levels thus holds promise for managing both early-stage and later-stage viral infections, including SARS-CoV-2. Using SARS-CoV-2 as a model for similar viral infections, here we explore the current evidence regarding nitric oxide and hydrogen sulfide's use to limit viral infection, resolve inflammation, and reduce vascular and pulmonary damage.

Long-term consumption of beetroot juice on efficacy of converting dietary nitrate to plasma nitrate and nitrite was investigated. Adults were randomized to consume either beetroot juice with 380 mg of nitrate (BR) or a beetroot juice placebo (PL) for 12-weeks. Plasma nitrate and nitrite were measured before and 90-minutes after consuming their intervention beverage. Percent change in nitrite across the 90 min was greater in BR (273.2 ± 39.9%) vs. PL (4.9 ± 36.9%). Long-term consumption of nitrate containing beetroot juice increased fasting nitrate and nitrite plasma levels compared to baseline.

Color pigments from plant, animal, or mineral sources can be identified, separated, and quantified for various purposes. It is expected that pigments from Beta vulgaris L. peels and pomaces could be used to develop natural dyes that can find applications in areas such as food or textile dyeing industries. This work aimed at identifying and quantifying the pigment in the B. vulgaris L. peels and pomaces extracts as well as validating the method by high-performance liquid chromatography combined with ultraviolet spectroscopy (HPLC-UV) and ultra-high-performance liquid chromatography coupled with triple quadrupole (TSQ) mass spectrometry (UHPLC-MS/MS). Column chromatography was used to isolate compounds after methanolic solvent extraction. Identification and quantification of the pigments in the extract were achieved using reverse-phase HPLC with a UV detector (538 nm). The UHPLC-MS/MS was used for further confirmation of colored compounds in the extract. Method validation included the use of betanin standard (betanidin 5-β-D-glucopyranoside), determination of repeatability (precision), calibration curve linearity, and sensitivity (LOD and LOQ) tests. Betanin was detected in the sample at retention times of 7.699 and 7.71 minutes, respectively, which closely matched the tR (7.60 min) of the standard, according to HPLC-UV and LC-MS/MS data. The average betanin concentration was 3.81 0.31 mg/g of dry weight, according to the HPLC-UV analysis. The LC-MS/MS data revealed the existence of several compounds, including betanin (4.31 ± 2.15 mg/g), isobetanin (1.85 ± 2.20 mg/g), 2, 17-bidecarboxy-neobetanin (0.71 ± 0.02 mg/g), betanidin (0.71 ± 0.03 mg/g), 2-O-glucosyl-betanin (0.40 ± 0.10 mg/g), and isobetanidin (0.36 ± 1.26 mg/g), among other compounds whose yields were too low. In conclusion, the peels and pomaces of B. vulgaris L. can be a useful source for the extraction of a red dye for use in coloring, such as the dyeing of textile substrates.

Non-alcoholic steatohepatitis (NASH) is a progressive subtype of non-alcoholic fatty liver disease (NAFLD) that is closely related to cardiovascular disease (CVD). Nitric oxide (NO) plays a critical role in the control of various biological processes. Dysfunction of the NO signaling pathway is associated with various diseases such as atherosclerosis, vascular inflammatory disease, and diabetes. Recently, it has been reported that NO is related to lipid and cholesterol metabolism. Chronic NO synthase (NOS) inhibition accelerates NAFLD by increasing hepatic lipid deposition. However, the detailed relationship between NO and abnormal lipid and cholesterol metabolism in NAFLD/NASH has not been completely explained. We aimed to determine the effects of NOS inhibition by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME), a NOS inhibitor, on NASH and CVD via lipid and cholesterol metabolism.

Stroke-prone spontaneously hypertensive rats were fed a high-fat and high-cholesterol diet for 8 weeks and administered L-NAME for the last 2 weeks. Following blood and tissue sampling, biochemical analysis, histopathological staining, quantitative RT-PCR analysis, and western blotting were performed.

L-NAME markedly increased hepatic triglyceride (TG) and cholesterol levels by promoting TG synthesis and cholesterol absorption from the diet. L-NAME increased the mRNA levels of inflammatory markers and fibrotic areas in the liver. Cholesterol secretion from the liver was promoted in rats administered L-NAME, which increased serum cholesterol. L-NAME significantly increased the level of oxidative stress marker and lipid deposition in the arteries.

NOS inhibition simultaneously aggravates NASH and atherosclerosis via hepatic lipid and cholesterol metabolism.