Reduced nitric oxide synthesis in winter: A potential contributing factor to increased cardiovascular risk

Liddle, Luke; Monaghan, Christopher; Burleigh, Mia; Baczynska, K.; Muggeridge, David J.; Easton, Chris

doi:10.1016/j.niox.2022.06.007

Cited by 14 publications

(7 citation statements)

References 69 publications

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“…The average nitrite levels were around 350 times lower (134 nmol/L at BL and 136 nmol/L at D90). In two studies with systemically healthy individuals recruited at the same location (Glasgow, Scotland, United Kingdom), similar plasma nitrate and nitrite levels were found in a fasting state: Burleigh et al 50 found averages of 34 μmol/L nitrate and 133 nmol/L nitrite in 25 individuals, while Liddle et al 51 found averages of 54 μmol/L nitrate and 137 nmol/L nitrite in 34 individuals. It is known that nitrate intake increases the plasma nitrate and nitrite concentrations multiple times, 17 indicating that at the timing of sample collection in our study, no dietary nitrate metabolism was detected.…”

Section: Discussionmentioning

confidence: 75%

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability

Rosier

Johnston

Carda‐Diéguez

et al. 2023

Preprint

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Background: The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions, such as hypertension and diabetes. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with healthy conditions, but the impact of periodontitis on nitrate-reducing capacity and therefore nitric oxide availability has not been evaluated. The aim of the current study is to see assess how periodontitis and periodontal treatment affect the nitrate reduction capacity of the oral microbiota. Methods: First, 16S rRNA sequencing data of five studies from different countries were analysed with the Dada2 pipeline to compare nitrate-reducing bacteria in health and periodontitis. Additionally, subgingival plaque, saliva and plasma samples from 42 periodontitis patients were collected before and after non-surgical periodontal therapy (NSPT). The subgingival plaque bacterial composition was determined using Illumina sequencing of the 16S rRNA gene and the quantity of the nitrate-reducing biomarker genus Rothia was determined by qPCR. Measurements of nitrate and nitrite in saliva and plasma were performed and the salivary nitrate reduction capacity (NRC) was determined after three hours of incubation in vitro and compared with the NRC of 15 healthy individuals. Results: Nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (p < 0.05 in all five datasets). After NSPT, nitrate-reducing bacteria increased in subgingival plaque (p < 0.05) and correlated negatively with periodontitis-associated bacteria (p < 0.001). A post-treatment increase in the genus Rothia was confirmed by qPCR (p < 0.05), as well as an increase in the salivary NRC (p < 0.05). No significant effect was found of NSPT on the plasma nitrate and nitrite levels in this population. Conclusion: The levels of nitrate-reducing bacteria of the subgingival microbiota decrease in periodontitis and both their levels and the salivary NRC increase after NSPT. We hypothesize that an impaired NRC can affect nitric oxide availability and can therefore be an instrumental link between periodontitis and systemic conditions.

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Section: Discussionmentioning

confidence: 75%

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability

Rosier

Johnston

Carda‐Diéguez

et al. 2023

Preprint

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“…Nitric oxide (NO) is a gaseous signaling molecule crucial for maintaining vascular homeostasis. The synthesis of NO occurs when L-arginine is converted by nitric oxide synthases (NOS) in the presence of oxygen [135]. The plasma nitrite levels, a well-known indicator of NO production, exhibit a higher concentration in healthy individuals during the summer compared to the winter.…”

Section: L-cysteine Nitric Oxide Hydrogen Sulfide and Vitamin D Metab...mentioning

confidence: 99%

The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency

Jain,

Justin Margret,

Abrams

et al. 2024

Nutrients

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Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.

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“…One potential benefit of exposure to UV-A radiation is to promote non-enzymatic production of nitric oxide (NO) by the skin (Monaghan et al, 2018 ). This can have beneficial effects in lowering blood pressure (Liddle et al, 2022 ). The current aimed to see if metabolomic changes linked to UV exposure to which might indicate effects on NO production.…”

Section: Introductionmentioning

confidence: 99%

LC/MS-based discrimination between plasma and urine metabolomic changes following exposure to ultraviolet radiation by using data modelling

Ali

Monaghan²,

Muggeridge³

et al. 2023

Metabolomics

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Introduction This study sought to compare between metabolomic changes of human urine and plasma to investigate which one can be used as best tool to identify metabolomic profiling and novel biomarkers associated to the potential effects of ultraviolet (UV) radiation. Method A pilot study of metabolomic patterns of human plasma and urine samples from four adult healthy individuals at before (S1) and after (S2) exposure (UV) and non-exposure (UC) were carried out by using liquid chromatography-mass spectrometry (LC–MS). Results The best results which were obtained by normalizing the metabolites to their mean output underwent to principal components analysis (PCA) and Orthogonal Partial least squares-discriminant analysis (OPLS-DA) to separate pre-from post-of exposure and non-exposure of UV. This separation by data modeling was clear in urine samples unlike plasma samples. In addition to overview of the scores plots, the variance predicted-Q2 (Cum), variance explained-R2X (Cum) and p-value of the cross-validated ANOVA score of PCA and OPLS-DA models indicated to this clear separation. Q2 (Cum) and R2X (Cum) values of PCA model for urine samples were 0.908 and 0.982, respectively, and OPLS-DA model values were 1.0 and 0.914, respectively. While these values in plasma samples were Q2 = 0.429 and R2X = 0.660 for PCA model and Q2 = 0.983 and R2X = 0.944 for OPLS-DA model. LC–MS metabolomic analysis showed the changes in numerous metabolic pathways including: amino acid, lipids, peptides, xenobiotics biodegradation, carbohydrates, nucleotides, Co-factors and vitamins which may contribute to the evaluation of the effects associated with UV sunlight exposure. Conclusions The results of pilot study indicate that pre and post-exposure UV metabolomics screening of urine samples may be the best tool than plasma samples and a potential approach to predict the metabolomic changes due to UV exposure. Additional future work may shed light on the application of available metabolomic approaches to explore potential predictive markers to determine the impacts of UV sunlight.

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Reduced nitric oxide synthesis in winter: A potential contributing factor to increased cardiovascular risk

Cited by 14 publications

References 69 publications

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability

The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency

LC/MS-based discrimination between plasma and urine metabolomic changes following exposure to ultraviolet radiation by using data modelling

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