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

Clifford, Tom; Babateen, Abrar; Shannon, Oliver Michael; Capper, Tess; Ashor, Ammar W.; Stephan, Blossom C. M.; Robinson, Louise; O’Hara, John; Mathers, John C.; Stevenson, Emma; Siervo, Mario

doi:10.1080/10408398.2018.1453779

Cited by 33 publications

(40 citation statements)

References 38 publications

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“…In contrast with our results, multiple studies show no significant association with foods containing nitrate and changes in cognitive function or mood [54][55][56][57][58][59][60] . Possible factors contributing to conflicting cognitive responses reports and our own study include different routes of treatment (continual in water vs episodic in meals), different nitrate doses and lengths of treatment, food matrix effects, age and health status of participants, or unidentified species-specific effects.…”

Section: Discussioncontrasting

confidence: 99%

Nitrate and nitrite exposure increases anxiety-like behavior and alters brain metabolomic profile in zebrafish

García-Jaramillo

Beaver

Truong

et al. 2020

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IntroductionDietary nitrate lowers blood pressure and improves athletic performance in humans, yet data supporting observations that it may increase cerebral blood flow and improve cognitive performance are mixed. Here we tested the hypothesis that nitrate and nitrite treatment would improve indicators of learning and cognitive performance in a zebrafish (Danio rerio) model. We also explored the extent to which nitrate and nitrite treatment affected the brain metabolome in order to understand how nitrate and nitrite supplementation may affect indices of cognitive function.MethodsFish were exposed to sodium nitrate (606.9 mg/L), sodium nitrite (19.5 mg/L), or control water for 2-4 weeks and free swim, startle response, innate predator avoidance, social cohesion, and shuttle box assays were performed.ResultsNitrate and nitrite treatment did not change fish weight, length, predator avoidance, or distance and velocity traveled in an unstressed environment. Nitrate- and nitrite-treated fish initially experienced more negative reinforcement and increased time to decision in the shuttle box assay, which is consistent with a decrease in associative learning or executive function however, over multiple trials, all treatment groups demonstrated behaviors associated with learning. Nitrate and nitrite treatment significantly increased anxiety-like behavior but did not alter epinephrine, norepinephrine or dopamine levels. Targeted LC-MS/MS analysis revealed no significant increase in brain nitrate or nitrite concentrations with treatment. An untargeted metabolomics analysis found 47 metabolites whose abundance was significantly altered in the brain with nitrate and nitrite treatment including an 18-19% reduction in the neurotransmitter γ-aminobutyric acid (GABA), and 17-22% reduction in its precursor, glutamine, which may contribute to the increased anxiety-like behavior.ConclusionNitrate and nitrite treatment did not adversely affect multiple parameters of zebrafish health but was associated with mild anxiety-like behavior, changes in the brain metabolome, and caused a short-term decrease in executive function or associative learning.

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Section: Discussioncontrasting

confidence: 99%

Nitrate and nitrite exposure increases anxiety-like behavior and alters brain metabolomic profile in zebrafish

García-Jaramillo

Beaver

Truong

et al. 2020

Preprint

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“…Interestingly, in some areas, the nutrition professionals surveyed were more optimistic about beneficial effects of nitrate than justified by the present state of the knowledge. Over a quarter of participants believed that inorganic nitrate improves cognitive function, despite the lack of consistent evidence to support this notion,33–38 and a recent meta-analysis reporting no overall effect of nitrate on cognition or cerebral blood flow 30. Similarly, almost a quarter of participants claimed that nitrate improved lung function, despite little evidence existing to support this notion 39 40.…”

Section: Discussionmentioning

confidence: 99%

“…Questions where current evidence is ambiguous or where there is no correct response (ie, the answer reflects a belief or opinion on inorganic nitrate) were not included in the Index. Recently published systematic reviews and meta-analyses were used to inform these decisions 17 24 30 31…”

Section: Methodsmentioning

confidence: 99%

Knowledge and beliefs about dietary inorganic nitrate among UK-based nutrition professionals: development and application of the KINDS online questionnaire

et al. 2019

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ObjectivesTo examine knowledge and beliefs about the biological roles of dietary inorganic nitrate in UK-based nutrition professionals, and to explore potential differences by participants’ education level.SettingAn online questionnaire was administered to UK-based nutrition professionals, exploring knowledge and/or beliefs across five areas: (1) health and performance effects of nitrate; (2) current and recommended intake values for nitrate; (3) dietary sources of nitrate; (4) methods of evaluating nitrate intake and (5) nitrate metabolism.ParticipantsOne hundred and twenty-five nutrition professionals.Primary outcomeKnowledge and beliefs about inorganic nitrate.ResultsMost nutrition professionals taking part in the survey had previously heard of inorganic nitrate (71%) and perceived it to be primarily beneficial (51%). The majority believed that nitrate consumption can improve sports performance (59%) and reduce blood pressure (54%), but were unsure about effects on cognitive function (71%), kidney function (80%) and cancer risk (70%). Knowledge of dietary sources of nitrate and factors affecting its content in food were generally good (41%–79% of participants providing correct answers). However, most participants were unsure of the average population intake (65%) and the acceptable daily intake (64%) of nitrate. Most participants (65%) recognised at least one compound (ie, nitric oxide or nitrosamines) that is derived from dietary nitrate in the body. Knowledge of nitrate, quantified by a 23-point index created by summing correct responses, was greater in individuals with a PhD (p=0.01; median (IQR)=13 (9–17)) and tended to be better in respondents with a masters degree (p=0.054; 13 (8–15)) compared with undergraduate-level qualifications (10 (2–14)).ConclusionsUK-based nutrition professionals demonstrated mixed knowledge about the physiology of dietary nitrate, which was better in participants with higher education. More efficient dissemination of current knowledge about inorganic nitrate and its effects on health to nutrition professionals will support them to make more informed recommendations about consumption of this compound.

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“…Current evidence, which is principally derived from observational studies, has identified numerous dietary factors associated with better cognitive performance, with cell and mouse models providing insights into underlying physiological and molecular mechanisms (Vauzour et al 2017; Scarmeas et al 2018). Nutritional compounds which have attracted attention for their potential to improve cognition include the n ‐3 fatty acid, docosahexaenoic acid (DHA) (Dyall 2015), B vitamins (Luchsinger et al 2007; Lefèvre‐Arbogast et al 2016), plant‐derived flavonoids (Commenges et al 2000; Letenneur et al 2007), vitamin D (Anastasiou et al 2014) and, inconsistently, inorganic nitrate (Gilchrist et al 2014; Shannon et al 2017; Clifford et al 2019). However, comprehensive longitudinal data, combining sensitive neural biomarkers ( e.g.…”

Section: Nutrition and Healthy Brain Ageingmentioning

confidence: 99%

NuBrain: UK consortium for optimal nutrition for healthy brain ageing

et al. 2020

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With an ageing global population, there is an urgent need to identify effective strategies to maintain brain health across the life course and therein minimise the risk of age-related neurodegenerative disorders reaching a severe stage which may manifest as dementia. An increasing body of evidence indicates that nutrition is a modifiable lifestyle factor that can promote healthy brain ageing and reduce dementia risk. However, at present, little is known about which dietary patterns, foods and food bioactives influence brain function during ageing, and more research is required to identify at-risk individuals and population subgroups who are most likely to benefit from future nutritional intervention intended to promote healthier brain ageing. This article introduces the newly established Medical Research Council-funded NuBrain consortium, the vision of which is to provide a step change in research in the area by developing novel approaches and techniques to further understand the complex interactions between diet and brain health and how we can support appropriate behaviour changes in the population. NuBrain will form a new, sustainable and internationally field-leading research consortium with multidisciplinary and complementary areas of expertise to address the fundamental research challenges in this area.

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

Cited by 33 publications

References 38 publications

Nitrate and nitrite exposure increases anxiety-like behavior and alters brain metabolomic profile in zebrafish

Nitrate and nitrite exposure increases anxiety-like behavior and alters brain metabolomic profile in zebrafish

Knowledge and beliefs about dietary inorganic nitrate among UK-based nutrition professionals: development and application of the KINDS online questionnaire

NuBrain: UK consortium for optimal nutrition for healthy brain ageing

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