Impact of Dietary Nitrate Supplementation on Executive Function During Hypoxic Exercise

Dobashi, Shohei; Koyama, Katsuhiro; Endo, Junko; Kiuchi, Masataka; Horiuchi, Masahiro

doi:10.1089/ham.2018.0114

Cited by 9 publications

(5 citation statements)

References 25 publications

(37 reference statements)

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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

Preprint

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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

View full text Add to dashboard Cite

show abstract

“…These brain regions participate in executive function, which may have been affected by nitrate and nitrite treatment in our study. In contrast with our results, multiple studies show no significant association with foods containing nitrate and changes in cognitive function or mood [49][50][51][52][53][54][55]. 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: Plos Onecontrasting

confidence: 99%

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“…A commercially available hypoxic generator (b-Cat ALT-120, B-cat High Altitude, Tiel, the Netherlands) is used, which is similar to devices regularly used in hypoxic training studies [26][27][28][29][30][31][32][33][34][35][36][37][38]. The intervention will be primarily administered at the participant's home.…”

Section: Interventional Medical Devicementioning

confidence: 99%

Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol

Janssen Daalen,

Meinders,

Mathur

et al. 2024

BMC Neurol

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Background Parkinson’s disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD. Methods/Design : This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction. Discussion This trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD. Trial registration ClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).

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Impact of Dietary Nitrate Supplementation on Executive Function During Hypoxic Exercise

Cited by 9 publications

References 25 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

Untitled

Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol

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