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Sports Medicine (Auckland, N.Z.) May 2014Dietary nitrate is growing in popularity as a sports nutrition supplement. This article reviews the evidence base for the potential of inorganic nitrate to enhance... (Review)
Review
Dietary nitrate is growing in popularity as a sports nutrition supplement. This article reviews the evidence base for the potential of inorganic nitrate to enhance sports and exercise performance. Inorganic nitrate is present in numerous foodstuffs and is abundant in green leafy vegetables and beetroot. Following ingestion, nitrate is converted in the body to nitrite and stored and circulated in the blood. In conditions of low oxygen availability, nitrite can be converted into nitric oxide, which is known to play a number of important roles in vascular and metabolic control. Dietary nitrate supplementation increases plasma nitrite concentration and reduces resting blood pressure. Intriguingly, nitrate supplementation also reduces the oxygen cost of submaximal exercise and can, in some circumstances, enhance exercise tolerance and performance. The mechanisms that may be responsible for these effects are reviewed and practical guidelines for safe and efficacious dietary nitrate supplementation are provided.
Topics: Athletic Performance; Dietary Supplements; Energy Metabolism; Exercise; Exercise Tolerance; Humans; Muscle, Skeletal; Nitrates; Oxygen Consumption; Sports Nutritional Physiological Phenomena
PubMed: 24791915
DOI: 10.1007/s40279-014-0149-y -
The American Journal of Clinical... Jul 2009The presence of nitrates and nitrites in food is associated with an increased risk of gastrointestinal cancer and, in infants, methemoglobinemia. Despite the physiologic... (Review)
Review
The presence of nitrates and nitrites in food is associated with an increased risk of gastrointestinal cancer and, in infants, methemoglobinemia. Despite the physiologic roles for nitrate and nitrite in vascular and immune function, consideration of food sources of nitrates and nitrites as healthful dietary components has received little attention. Approximately 80% of dietary nitrates are derived from vegetable consumption; sources of nitrites include vegetables, fruit, and processed meats. Nitrites are produced endogenously through the oxidation of nitric oxide and through a reduction of nitrate by commensal bacteria in the mouth and gastrointestinal tract. As such, the dietary provision of nitrates and nitrites from vegetables and fruit may contribute to the blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) diet. We quantified nitrate and nitrite concentrations by HPLC in a convenience sample of foods. Incorporating these values into 2 hypothetical dietary patterns that emphasize high-nitrate or low-nitrate vegetable and fruit choices based on the DASH diet, we found that nitrate concentrations in these 2 patterns vary from 174 to 1222 mg. The hypothetical high-nitrate DASH diet pattern exceeds the World Health Organization's Acceptable Daily Intake for nitrate by 550% for a 60-kg adult. These data call into question the rationale for recommendations to limit nitrate and nitrite consumption from plant foods; a comprehensive reevaluation of the health effects of food sources of nitrates and nitrites is appropriate. The strength of the evidence linking the consumption of nitrate- and nitrite-containing plant foods to beneficial health effects supports the consideration of these compounds as nutrients.
Topics: Animals; Diet; Food Analysis; Food Handling; Fruit; Health; Humans; Meat; Nitrates; Nitric Oxide; Nitrites; Vegetables
PubMed: 19439460
DOI: 10.3945/ajcn.2008.27131 -
Cardiovascular Drugs and Therapy Aug 2016Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic... (Review)
Review
Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K(+) ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.
Topics: Angina, Stable; Humans; Nicorandil; Nitrates; Nitric Oxide Donors; Vasodilator Agents
PubMed: 27311574
DOI: 10.1007/s10557-016-6668-z -
Molecules (Basel, Switzerland) Sep 2014Nitric oxide (NO) is one of the most important vasodilator molecules produced by the endothelium. It has already been established that NO/cGMP signaling pathway... (Review)
Review
Nitric oxide (NO) is one of the most important vasodilator molecules produced by the endothelium. It has already been established that NO/cGMP signaling pathway deficiencies are involved in the pathophysiological mechanisms of many cardiovascular diseases. In this context, the development of NO-releasing drugs for therapeutic use appears to be an effective alternative to replace the deficient endogenous NO and mimic the role of this molecule in the body. Organic nitrates represent the oldest class of NO donors that have been clinically used. Considering that tolerance can occur when these drugs are applied chronically, the search for new compounds of this class with lower tolerance potential is increasing. Here, we briefly discuss the mechanisms involved in nitrate tolerance and highlight some achievements from our group in the development of new organic nitrates and their preclinical application in cardiovascular disorders.
Topics: Humans; Nitrates; Nitric Oxide Donors; Organic Chemicals
PubMed: 25255247
DOI: 10.3390/molecules190915314 -
Methodist DeBakey Cardiovascular Journal 2019Nitric oxide (NO) is continually produced by the enzyme nitric oxide synthase (NOS) and is essential to the control and effectiveness of the cardiovascular system.... (Review)
Review
Nitric oxide (NO) is continually produced by the enzyme nitric oxide synthase (NOS) and is essential to the control and effectiveness of the cardiovascular system. However, there is a substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular complications. Fortunately, NO can also be produced by the sequential reduction of inorganic nitrate to nitrite and then to NO. Nitric oxide from inorganic nitrate supplementation has been found to have the same cardioprotective benefits of NO produced by NOS. Moreover, it can effectively compensate for declining NOS activity due to aging or NOS inhibition by oxidative stress, hypoxia, or other factors. This review covers some of the major cardiovascular regulatory actions of NO and presents evidence that NO from inorganic nitrate supplementation can provide (1) compensation when NOS activity is inadequate, and (2) cardioprotective benefits beyond that provided by a healthy NOS system. In addition, it discusses how to obtain a safe and efficacious range of inorganic nitrate.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Dietary Supplements; Health Status; Humans; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Risk Factors; Treatment Outcome
PubMed: 31687099
DOI: 10.14797/mdcj-15-3-200 -
Environment International Dec 2021The impacts of dietary nitrates and nitrites on human health have been a controversial topic for many years. However, the risk and benefit assessment of nitrates and...
Probabilistic risk and benefit assessment of nitrates and nitrites by integrating total diet study-based exogenous dietary exposure with endogenous nitrite formation using toxicokinetic modeling.
The impacts of dietary nitrates and nitrites on human health have been a controversial topic for many years. However, the risk and benefit assessment of nitrates and nitrites is complicated by the large variation in nitrate and nitrite intake among people and the endogenous nitrite formation in the body. This study conducted a probabilistic risk-benefit assessment of dietary nitrates and nitrites based on internal dose by integrating exogenous and endogenous exposures with human trial data on cardiovascular benefits. A total diet study was carried out to quantify the age-specific dietary intakes of nitrates and nitrites. A previously well-validated human toxicokinetic model was used to predict internal doses for different age groups. In addition, the integrated approach was applied to different populations from different countries/regions based on reported exposure estimates to conduct a comprehensive risk-benefit assessment of dietary nitrates and nitrites. The results demonstrated that vegetable consumption was the main contributor to the internal nitrate and nitrite levels in all age groups. Exposure to nitrates and nitrites exceeding acceptable daily intakes in a variety of foods showed cardiovascular benefits. The probabilistic risk assessment showed that the exposure to nitrates and nitrites did not pose an appreciable health and safety risk. Therefore, the present results suggest that dietary nitrates and nitrites have clear cardiovascular benefits that may outweigh potential risks. Our analysis contributes significantly to addressing the controversy regarding risks and benefits from dietary nitrates and nitrites, and our approach could be applied to other dietary constituents with the potential for both risks and benefits.
Topics: Diet; Dietary Exposure; Humans; Nitrates; Nitrites; Toxicokinetics
PubMed: 34418847
DOI: 10.1016/j.envint.2021.106807 -
British Journal of Pharmacology Jan 2019Inorganic nitrate (NO ), nitrite (NO ) and NO are nitrogenous species with a diverse and interconnected chemical biology. The formation of NO from nitrate and nitrite... (Review)
Review
Inorganic nitrate (NO ), nitrite (NO ) and NO are nitrogenous species with a diverse and interconnected chemical biology. The formation of NO from nitrate and nitrite via a reductive 'nitrate-nitrite-NO' pathway and resulting in vasodilation is now an established complementary route to traditional NOS-derived vasodilation. Nitrate, found in our diet and abundant in mammalian tissues and circulation, is activated via reduction to nitrite predominantly by our commensal oral microbiome. The subsequent in vivo reduction of nitrite, a stable vascular reserve of NO, is facilitated by a number of haem-containing and molybdenum-cofactor proteins. NO generation from nitrite is enhanced during physiological and pathological hypoxia and in disease states involving ischaemia-reperfusion injury. As such, modulation of these NO vascular repositories via exogenously supplied nitrite and nitrate has been evaluated as a therapeutic approach in a number of diseases. Ultimately, the chemical biology of nitrate and nitrite is governed by local concentrations, reaction equilibrium constants, and the generation of transient intermediates, with kinetic rate constants modulated at differing physiological pH values and oxygen tensions. LINKED ARTICLES: This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc.
Topics: Animals; Humans; Hydrogen-Ion Concentration; Kinetics; Nitrates; Nitric Oxide; Nitrites; Oxygen; Signal Transduction
PubMed: 30152056
DOI: 10.1111/bph.14484 -
The Western Journal of Medicine Jan 1981Cases of acquired methemoglobinemia have been identified with increasing frequency in Los Angeles during the last several years. Among 18 patients, both infants and...
Cases of acquired methemoglobinemia have been identified with increasing frequency in Los Angeles during the last several years. Among 18 patients, both infants and adults, the most commonly incriminated agent was silver nitrate used for topical antibacterial prophylaxis of burn wounds. One burned child died from overwhelming septicemia complicated by hypoxia with a methemoglobin level of 5.4 grams per dl. Other causative factors included nitrate-rich vegetables used in early infancy, additives in ethnic foods, and prescribed and overdosed drugs. Discontinuation of the precipitating agent and methylene blue therapy were usually followed by prompt improvement. In burned patients treated with silver nitrate, careful regular monitoring of serum methemoglobin levels and early initiation of specific therapy are mandatory.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Methemoglobinemia; Middle Aged; Nitrates; Nitrites; Silver Nitrate
PubMed: 7210666
DOI: No ID Found -
Cardiology Journal 2009Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid... (Review)
Review
Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid development of nitrate tolerance, limiting their hemodynamic and anti-ischemic efficacy. In addition, nitrate tolerance is associated with the expression of potentially deleterious modifications such as increased oxidative stress, endothelial dysfunction, and sympathetic activation. In this review we discuss current concepts regarding the mechanisms of organic nitrate bioactivation, nitrate tolerance, and nitrate-mediated oxidative stress and endothelial dysfunction. We also examine how hydralazine may prevent nitrate tolerance and related endothelial dysfunction.
Topics: Aldehyde Dehydrogenase; Biotransformation; Drug Therapy, Combination; Drug Tolerance; Endothelium, Vascular; Ethanol; Humans; Hydralazine; Mitochondria; Nitrates; Oxidative Stress; Reactive Oxygen Species; Sympathetic Nervous System; Tachyphylaxis; Vasodilation; Vasodilator Agents
PubMed: 19130411
DOI: No ID Found -
International Journal of Environmental... Sep 2022Recovery between efforts is critical to achieving optimal physical and sports performance. In this sense, many nutritional supplements that have been proven to improve... (Review)
Review
BACKGROUND
Recovery between efforts is critical to achieving optimal physical and sports performance. In this sense, many nutritional supplements that have been proven to improve recovery and physical and physiological performance are widely used. Supplements such as nitrates (NO), including organic foods such as beets, promote muscle recovery and relieve fatigue. This study aimed to comprehensively summarise the available literature on the effect of NO consumption on exercise-related fatigue and muscle damage.
METHODS
A systematic search was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) using electronic databases (e.g., PubMed, Scopus, and Web of Science). From a total of 1634 studies identified, 15 studies were included in this review.
RESULTS
Based on the review, NO intake provokes physiological and metabolic responses that could potentially boost exercise-related recovery. NO could improve recovery indicators related to strength, pain, inflammation, and muscle damage.
CONCLUSIONS
Despite the relative proven effectiveness of NO on recovery after aerobic and anaerobic efforts, based on the heterogeneity of the procedures (e.g., dosage, chronic vs. acute intake, participants' characteristics, variables and outcomes), it could be premature to suggest its extended use in sports.
Topics: Athletic Performance; Dietary Supplements; Exercise; Humans; Muscle Fatigue; Nitrates
PubMed: 36231323
DOI: 10.3390/ijerph191912021