Dietary salt concentrations influence growth, nutrient utilization, and fatty acid profiles of turbot (Scophthalmus maximus) reared in brackish water.

Expansion of economically viable turbot (Scophthalmus maximus) aquaculture depends on access to brackish-cold ground water sources in various parts of the world. Since brackish water sources can adversely affect the physiology and zoo technical performance of fish due to the burden of osmoregulation, dietary salt inclusion can alleviate the negative impacts of low-saline waters in several aquaculture species. This study investigated the effects of increasing dietary salt levels on the growth, feed utilization, body composition, and tissue fatty acid composition of juvenile turbot (initial live weight 120.3 ± 0.03 g/fish). Fish were fed five experimental diets supplemented with varying levels of sodium chloride (1.8-6.4%) or a control diet without salt. Each diet was tested in triplicate tanks for 9 weeks. Results showed that increasing dietary salt intake negatively impacted turbot performance, with significant reductions in weight gain, specific growth rate, and feed conversion ratio. Dry matter and ash content in the whole body and filet increased quadratically with increasing salt levels, whereas gill moisture and protein content decreased linearly. Furthermore, the nitrogen, lipid, and energy utilization efficiencies decreased with their respective intake and gain levels. Dietary salt significantly influenced the fatty acid profiles of gill, liver, and filet tissues. In the gill, monounsaturated fatty acids (16:1n-7, ΣMUFA) and n-6 PUFA (20:2n-6) increased, whereas EPA and DHA decreased. Liver ΣSFA (16:0, 18:0) increased, and n-3 PUFA (18:3n-3, 20:5n-3) decreased with increasing dietary salt. Filet saturated fatty acids (14:0, 15:0, 17:0) and n-6 PUFA (20:2n-6, 20:4n-6) increased, while n-3 PUFA (18:3n-3, EPA) decreased with dietary salt. DHA levels in filets showed a quadratic increase. Overall, this study shows that increasing dietary salt negatively impacts turbot growth, feed utilization, and tissue fatty acid composition in brackish water, highlighting the need for further studies on salinity management strategies for turbot aquaculture.

Dietary salt promotes cognitive impairment through repression of SIRT3/PINK1-mediated mitophagy and fission.

Dietary salt is increasingly recognized as an independent risk factor for cognitive impairment. However, the exact mechanisms are not yet fully understood. Mitochondria, which play a crucial role in energy metabolism, are implicated in cognitive function through processes such as mitochondrial dynamics and mitophagy. While mitochondrial dysfunction is acknowledged as a significant determinant of cognitive function, the specific relationship between salt-induced cognitive impairment and mitochondrial health has yet to be fully elucidated. Here, we explored the underlying mechanism of cognitive impairment of mice and N2a cells treated with high-salt focusing on the mitochondrial homeostasis with western blotting, immunofluorescence, electron microscopy, RNA sequencing, and more. We further explored the potential role of SIRT3 in salt-induced mitochondrial dysfunction and synaptic alteration through plasmid transfection and siRNA. High salt diet significantly inhibited mitochondrial fission and blocked mitophagy, leading to dysfunctional mitochondria and impaired synaptic plasticity. Our findings demonstrated that SIRT3 not only promote mitochondrial fission by modulating phosphorylated DRP1, but also rescue mitophagy through promoting PINK1/Parkin-dependent pathway. Overall, our data for the first time indicate that mitochondrial homeostasis imbalance is a driver of impaired synaptic plasticity in a cognitive impairment phenotype that is exacerbated by a long-term high-salt diet, and highlight the protective role of SIRT3 in this process.

Barriers and Facilitators to Dietary Salt Reduction Among Patients With Hypertension in Southern Nigeria: A Hospital-based Qualitative Study.

Introduction: Reduction in salt intake improves blood pressure control and reduces the risk of hypertension and other noncommunicable diseases (NCDs). However, salt intake remains high among Nigerians. This study aimed to identify barriers and facilitators to salt reduction among hypertensive patients attending a family medicine clinic in southern Nigeria. Methodology: A focussed group discussion (FGD) exploring patients' perceptions of the barriers and facilitators to salt reduction was conducted with 8 groups of purposefully selected 74 hypertensives who consumed excess dietary salt, stratified by age and sex, using an FGD guide. Thematic analysis was then performed using Nvivo® version 12 pro. Ethical approval was obtained from Irrua Specialist Teaching Hospital (ISTH), and written informed consent was obtained from the patients before the FGD. Results: Respondents had a mean age of 51.96 ± 8.98 years. The majority were females (47, 63.5%) and had uncontrolled blood pressure (66, 89.2%). Five major themes were identified, from which several minor themes emerged. Respondents rated their overall health as good but expressed concerns about their poor blood pressure control. Identified barriers to salt reduction included family pressure, ignorance, ready availability and affordability of salt and lack of affordable alternatives. Facilitators of salt reduction were measuring the amount of cooking salt, removing salt from the dining table and providing substitutes. Respondents, however, expressed willingness to reduce their salt consumption. Conclusion: The study identified barriers and facilitators to salt reduction. There is a need to create awareness of the safe amount of salt to be consumed and provide safe and readily available alternatives.

Perspectives on the involvement of the gut microbiota in salt-sensitive hypertension.

Salt-sensitivity hypertension (SSH) is an independent predictor of cardiovascular event-related death. Despite the extensiveness of research on hypertension, which covers areas such as the sympathetic nervous system, the renin-angiotensin system, the vascular system, and the immune system, its pathogenesis remains elusive, with sub-optimal blood pressure control in patients. The gut microbiota is an important component of nutritional support and constitutes a barrier in the host. Long-term high salt intake can lead to gut microbiota dysbiosis and cause significant changes in the expression of gut microbiota-related metabolites. Of these metabolites, short chain fatty acids (SCFAs), trimethylamine oxide, amino acids, bile acids, and lipopolysaccharide are essential mediators of microbe-host crosstalk. These metabolites may contribute to the incidence and development of SSH via inflammatory, immune, vascular, and nervous pathways, among others. In addition, recent studies, including those on the histone deacetylase inhibitory mechanism of SCFAs and the blood pressure-decreasing effects of H2S via vascular activation, suggest that several proteins and factors in the classical pathway elicit their effects through multiple non-classical pathways. This review summarizes changes in the gut microbiota and its related metabolites in high-salt environments, as well as corresponding treatment methods for SSH, such as diet management, probiotic and prebiotic use, antibiotic use, and fecal transplantation, to provide new insights and perspectives for understanding SSH pathogenesis and the development of strategies for its treatment.

The impact of high-salt diet on asthma in humans and mice: Effect on specific T-cell signatures and microbiome.

BACKGROUND: The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models. METHODS: Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24-h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite-induced allergic airway inflammation (AAI) fed with high-salt diet (HSD) or normal-salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach. RESULTS: In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD-fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2-TH17-biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung. CONCLUSIONS: High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD-induced T-cell lung profiles accompanied by alterations of gut and lung microbiome.

Metabolomics signature of blood pressure salt sensitivity and its link to cardiovascular disease: A dietary salt-intervention trial.

Individuals with a high degree of salt sensitivity (SS) have a greater risk of cardiovascular disease (CVD), but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear. This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs, based on the MetaSalt study, which was a dietary salt-intervention trial conducted at four centers in China in 2019. A total of 528 participants were recruited and underwent 3 days of baseline observations, a 10-day low-salt intervention, and a 10-day high-salt intervention. Plasma untargeted metabolomics, lipidomics, and BP measurements were scheduled at each stage. Participants were grouped into extreme SS, moderate SS, and salt-resistant (SR) individuals according to their BP responses to salt. Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness. Mendelian randomization (MR) analyses were applied to establish the causal pathways among the SS-related metabolites, BP, and CVDs. Among the 713 metabolites, 467 were significantly changed after the high-salt intervention. Among them, the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups. Of the remaining nonsalt-related metabolites, the baseline levels of 11 metabolites were related to SS. These 41 metabolites explained 23% of the variance in SS. Moreover, SS and its metabolomics signature were positively correlated with arterial stiffness. MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP, indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause. Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs. This study provides insight into understanding the biology and targets of SS and its role in CVDs.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

PURPOSE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score. CONCLUSIONS: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The potential for current sodium and potassium production to support a global switch to the use of potassium-enriched salt: a desktop research study.

OBJECTIVE: Switching regular salt (sodium chloride) to salt enriched with potassium chloride (25 % potassium chloride, 75 % sodium chloride) has been shown to reduce blood pressure and the risk of cardiovascular diseases. We sought to define the potential for the current production of sodium chloride and potassium chloride to support a global switch to the use of potassium-enriched salt. DESIGN: We summarised data from geological surveys, government reports and trade organisations describing the global production and supply of sodium chloride and potash (the primary source of potassium chloride) and compared this to potential requirements for potassium-enriched salt. SETTING: Global. PARTICIPANTS: Not applicable. RESULTS: Approximately 280 million tonnes of sodium chloride were produced in 2020 with China and the USA the main producers. Global production of potash from which potassium chloride is extracted was about forty-four million tonnes with Canada, Belarus, Russia and China providing 77 % of the world's supply. There were forty-eight countries in which potassium-enriched salt is currently marketed with seventy-nine different brands identified. Allowing for loss of salt between manufacture and consumption, a full global switch from regular salt to potassium-enriched salt would require about 9·7 million tonnes of sodium chloride to be replaced with 9·7 million tonnes of potassium chloride annually. CONCLUSIONS: Significant upscaling of the production of potassium chloride and the capacity of companies able to manufacture potassium-enriched salt, as well as a robust business case for the switch to potassium chloride, would be required.

Knowledge, attitudes, and practices related to dietary salt among older adults in Abha, Saudi Arabia.

The need to foster successful aging has intensified with the aging of the global population. This study aimed to assess the knowledge, attitudes, and practices (KAP) concerning dietary salt consumption and to investigate the correlations between sociodemographic variables and salt-related KAP. A structured interview was administered to a cohort of 200 older adults in Abha City, Saudi Arabia, recruited through a convenience sampling approach. The evaluation of salt-related KAP revealed widespread low knowledge (91.5%) as participants scored less than 3, negative attitudes (85.5%) scored less than 12, and predominantly unsatisfactory practices (69.5%) with scores less than 26. Noteworthy differences emerged between participants with poor overall KAP (81.5%) and those with good KAP (18.5%). Significantly weak negative correlations were found between age (r=-0.212), marital status (-0.236), and body mass index (-0.243) with overall KAP. Further examination revealed a significantly weak positive correlation between attitude and practice (r = 0.141). KAP scores show a highly significant positive correlation with overall KAP scores (r = 0.169, 0.352, 0.969). The uncovered correlations contribute to a valuable understanding of the complex dynamics surrounding salt-related KAP. This understanding guides the design of targeted interventions, such as health education programs, promoting successful aging and public health outcomes.

Dietary salt promotes cognition impairment through GLP-1R/mTOR/p70S6K signaling pathway.

Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction.

Erythrocyte glycocalyx sensitivity to sodium is associated with salt sensitivity of blood pressure in women but not men.

Background: While salt sensitivity of blood pressure (SSBP) is a risk factor for hypertension, end-organ damage and death, most studies are conducted in western countries and in White people. We previously found that the prevalence of SSBP in Blacks living in Sub-Saharan Africa is as high as 75-80% like what has been reported in the west. Erythrocyte glycocalyx sensitivity to sodium (eGCSS), a marker of sodium-induced damage to the erythrocyte and vascular endothelial glycocalyx is thought to be related to blood pressure perturbations associated with salt intake. We hypothesized that SSBP correlates with eGCSS differently in men and women in Black people. Methods: We conducted a cross sectional study using data from our recent clinical trial from Livingstone University Teaching Hospital among 117 normotensive young adults. We used a "salt blood test" to determine eGCSS and an immediate pressor response to oral salt (IPROS) for the diagnosis of SSBP. Results: The proportion of males were equal to females and the median age (interquartile range) of the participants was 29 (22-45) years. The eGCSS scores were higher in salt-resistant females compared to salt-sensitive females and males. eGCSS correlated negatively with SSBP (AOR 0.98, 95% CI 0.97-0.99, p = 0.008), however, this relationship was driven by female sex and abrogated by male sex. Although blood pressure elevations exhibited a sustained bimodal pattern in both sexes, in males, systolic and diastolic blood pressure never returned to baseline during the time course as it did in females. Conclusion: In this study, eGCSS correlated negatively with SSBP in black women but not in black men and the pressor response to dietary salt was significantly higher in men compared to women. These results suggest that women tend to have a higher disruption of the vascular endothelial glycocalyx by an acute salt load, implying that acute changes in blood pressure may not be driven directly by the endothelial glycocalyx. Our findings suggest a novel mechanism linking eGCSS and SSBP with potential implications for sex differences in salt-induced cardiovascular disease.Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT04844255].

Causal relationship between dietary salt intake and dementia risk: Mendelian randomization study.

OBJECTIVE: Observational research has indicated a potential link between dietary salt intake and susceptibility to dementia. However, it is important to note that these types of studies are prone to the issues of reverse causation and residual confounding. Therefore, we conducted a two-sample Mendelian randomization (MR) study to explore the causality. METHOD: To explore the causal relationship between them, this Mendelian randomization (MR) study incorporated summary statistics of dietary salt intake and dementia. We estimated the causality between salt intake and the risk of overall dementia and various subtypes of dementia, including Alzheimer's disease (AD), Vascular dementia (VaD), and Lewy body dementia (LBD). The inverse variance-weighted (IVW) method was the major MR analysis. To conduct sensitivity analyses, we employed various MR methods, the pleiotropy residual sum and outlier (MR-PRESSO) method, and the leave-one-out approach. The MR-Egger intercept and Cochran's Q test were conducted to test pleiotropy and heterogeneity respectively. RESULTS: A suggestive association was observed for genetically predicted higher dietary salt intake and increased risk of overall dementia in the European ancestry [odds ratio (OR): 1.542; 95% confidence interval (95% CI): 1.095-2.169; P = 0.013]. The causal relationship between dietary salt intake and overall dementia is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Meanwhile, no clear heterogeneity or pleiotropy was identified. However, we failed to detect a causal effect of dietary salt intake on the risk of various dementia subtypes. CONCLUSION: The results of this research present strong evidence that established a significant association between dietary salt intake and the likelihood of developing dementia. These findings reinforce the notion that the amount of dietary salt intake plays a crucial role in determining the risk of acquiring this cognitive condition. By establishing a definitive correlation, this study highlights the importance of reducing salt consumption as a preventive measure against dementia.

Dietary Salt Can Be Crucial for Food-Induced Vascular Inflammation.

Salt enhances the taste as well as the nutritional value of food. Besides, several reports are available on the incidence and epidemiology of various illnesses in relation to salt intake. Excessive salt consumption has been found to be linked with high blood pressure, renal disease, and other cardiovascular disorders due to the result of vascular inflammation. Nevertheless, studies aimed at elucidating the molecular processes that produce vascular inflammation have yet to reach their conclusions. This article emphasizes the significance of investigating the mechanisms underlying both acute and chronic vascular inflammation induced by salt. It also explores the logical inferences behind cellular oxidative stress and the role of endothelial dysfunction as the potential initiator of the inflammatory segments that remain poorly understood. It is therefore hypothesized that salt is one of the causes of chronic vascular inflammation such as atherosclerosis. The hypothesis's secrets, when revealed, can help assure cardiovascular health by proactive efforts and the development of appropriate preventative measures, in combination with medication, dietary and lifestyle adjustments.

TNF inhibits AQP2 expression via a miR137-dependent pathway.

As miR-137 is a regulator of aquaporin (AQP)2 expression and tumor necrosis factor (TNF) inhibits the expression of several extrarenal AQPs, we tested the hypothesis that TNF inhibits AQP2 in the kidney via a miR-137-dependent mechanism. AQP2 mRNA and protein expression decreased ∼70% and 53%, respectively, in primary renal inner medullary collecting duct (IMCD) cells transfected with a miRNA mimic of mmu-miR-137, suggesting that miR-137 directly targets AQP2 mRNA in these cells. Exposure of IMCD cells for 2 h to 400 mosmol/kgH2O medium increased mmu-miR-137 mRNA expression about twofold, conditions that also increased TNF production approximately fourfold. To determine if the increase in mmu-miR-137 mRNA expression was related to the concomitant increase in TNF, IMCD cells were transfected with a lentivirus construct to silence TNF. This construct decreased mmu-miR-137 mRNA expression by ∼63%, suggesting that TNF upregulates the expression of miR-137. Levels of miR-137 also increased approximately twofold in IMCD tubules isolated from male mice given 1% NaCl in the drinking water for 3 days. Intrarenal lentivirus silencing of TNF increased AQP2 mRNA levels and protein expression concomitant with a decrease in miR-137 levels in tubules isolated from mice given NaCl. The changes in AQP2 expression levels affected the diluting ability of the kidney, which was assessed by measuring urine osmolality and urine volume, as the decrease in these parameters after renal silencing of TNF was prevented on intrarenal administration of miR-137. The study reveals a novel TNF function via a miR-137-dependent mechanism that regulates AQP2 expression and function.NEW & NOTEWORTHY An emerging intratubular tumor necrosis factor system, functioning during normotensive noninflammatory conditions, acts as a breaking mechanism that attenuates both the increases in Na+-K+-2Cl- cotransporter and aquaporin-2 induced by arginine vasopressin, thereby contributing to the regulation of electrolyte balance and blood pressure. A greater appreciation for the role of cytokines as mediators of immunophysiological responses may help reveal the relationship between the immune system and other physiological systems.

Common salt aggravated pathology of testosterone-induced benign prostatic hyperplasia in adult male Wistar rat.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a major health concern associated with lower urinary tract symptoms and sexual dysfunction in men. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as a potential risk factor for BPH development or progression. This study examined the effect of common salt intake on the pathology of testosterone-induced BPH. METHODS: Forty male Wistar rats were randomly divided into four equal groups of 10: a control and three salt diet groups-low-salt diet (LSD), standard-salt diet (SSD) and high-salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt-free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injections of testosterone propionate-Testost® (3 mg/kg body weight) for 28 days. The rats had overnight fast (12 h) on day 60 and were euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated for each group and compared for significant difference with ANOVA followed by post hoc test (Tukey HSD) at p < 0.05. RESULTS: This study recorded a substantially higher level of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1ß, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-ß were similar in all the groups but there were multiple fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and multiple fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1) compared to control. Activity of superoxide dismutase (SOD) and concentration of nitric oxide rose in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC showed positive immunostaining for iNOS expression in all the groups while histopathology revealed moderate to severe prostatic hyperplasia in salt diet groups. CONCLUSIONS: These findings suggest that low, standard and high salt diets aggravated the pathology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, while suppressing apoptosis and angiogenesis.

India's tryst with salt: Dandi march to low sodium salts.

Salt plays a critical role in India's past as well as its present, from Dandi March to its role as a vehicle for micronutrient fortification. However, excess salt intake is a risk factor for high blood pressure and cardiovascular diseases (CVDs). Indians consume double the World Health Organization recommended daily salt (<5 g). India has committed to a 30 per cent reduction in sodium intake by 2025. Evidence based strategies for population sodium intake reduction require a moderate reduction in salt in - home cooked foods, packaged foods and outside-home foods. Reducing the sodium content in packaged food includes policy driven interventions such as front-of-package warning labels, food reformulation, marketing restrictions and taxation on high sodium foods. For foods outside of the home, setting standards for foods purchased and served by schemes like mid-day meals can have a moderate impact. For home cooked foods (the major source of sodium), strategies include advocacy for reducing salt intake. In addition to mass media campaigns for awareness generation, substituting regular salt with low sodium salt (LSS) has the potential to reduce salt intake even in the absence of a major shift in consumer behaviour. LSS substitution effectively lowers blood pressure and thus reduces the risk of CVDs. Further research is required on the effect of LSS substitutes on patients with chronic kidney disease. India needs an integrated approach to sodium reduction that uses evidence based strategies and can be implemented sustainably at scale. This will be possible only through scientific research, governmental leadership and a responsive evidence-to-action approach through a multi-stakeholder coalition.

Measured sodium excretion is associated with cardiovascular outcomes in non-dialysis CKD patients: results from the KNOW-CKD study.

Background: There are insufficient studies on the effect of dietary salt intake on cardiovascular (CV) outcomes in chronic kidney disease (CKD) patients, and there is no consensus on the sodium (Na) intake level that increases the risk of CV disease in CKD patients. Therefore, we investigated the association between dietary salt intake and CV outcomes in CKD patients. Methods: In the Korean cohort study for Outcome in patients with CKD (KNOW-CKD), 1,937 patients were eligible for the study, and their dietary Na intake was estimated using measured 24h urinary Na excretion. The primary outcome was a composite of CV events and/or all-cause death. The secondary outcome was a major adverse cardiac event (MACE). Results: Among 1,937 subjects, there were 205 (10.5%) events for the composite outcome and 110 (5.6%) events for MACE. Compared to the reference group (urinary Na excretion< 2.0g/day), the group with the highest measured 24h urinary Na excretion (urinary Na excretion ≥ 8.0g/day) was associated with increased risk of both the composite outcome (hazard ratio 3.29 [95% confidence interval 1.00-10.81]; P = 0.049) and MACE (hazard ratio 6.28 [95% confidence interval 1.45-27.20]; P = 0.013) in a cause-specific hazard model. Subgroup analysis also showed a pronounced association between dietary salt intake and the composite outcome in subgroups of patients with abdominal obesity, female, lower estimated glomerular filtration rate (< 60 ml/min per 1.73m2), no overt proteinuria, or a lower urinary potassium-to-creatinine ratio (< 46 mmol/g). Conclusion: A high-salt diet is associated with CV outcomes in non-dialysis CKD patients.

Evaluating the association between dietary salt intake and the risk of atrial fibrillation using Mendelian randomization.

Background: Previous studies have suggested that dietary salt intake affects atrial fibrillation (AF); however, the causal association between them still remains unclear. Thus, we conducted this Mendelian randomization (MR) study to explore the correlation between them. Methods: Genetic instruments for dietary salt intake were from a genome-wide association study (GWAS), which included 462,630 European individuals. Summary-level data for AF were obtained from another published GWAS (22,068 cases and 116,926 controls). The inverse-variance weighting (IVW) method was performed as the primary MR analysis. Multiple MR methods, including Robust Adjusted Profile Score (MR-RAPS), maximum likelihood estimation, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted as complementary analyses. The MR-Egger regression intercept and MR-PRESSO global test were conducted to test potential horizontal pleiotropy. The IVW (Q) method and MR-Egger were performed to detect heterogeneity. Results: Our results suggested that high dietary salt intake was significantly correlated with increased risk of AF [IVW: odds ratio (OR), 1.36; 95% confidence interval (CI), 1.04-1.77; p = 2.25E-02]. The maximum likelihood estimation (OR, 1.37; 95% CI, 1.05-1.78; p = 2.09E-02), MR-RAPS (OR, 1.37; 95% CI, 1.03-1.81; p = 2.79E-02), and MR-PRESSO method (OR, 1.36; 95% CI, 1.05-1.76; p = 2.37E-02) also showed that dietary salt intake was significantly correlated with the risk of AF. Conclusion: The findings of this study provide robust evidence supporting the correlation between dietary salt intake and the risk of AF. Future studies are required to further clarify this relationship and translate the findings into clinical and public health practice.

Design of a Nutritional Survey to Detect High Dietary Salt Intakes and Its Usefulness in Primary Care Compared to 24-Hour Urine Sodium Determination.

Many population studies report salt intakes that exceed the WHO recommendation (2 g/day of Na+ or 5 g/day of salt). We do not have tools for detecting high salt intakes that are easy to apply in primary health care (PHC). We propose the development of a survey to screen for high salt intake in PHC patients. A cross-sectional study of 176 patients determines the responsible foods, and a study of 61 patients studies the optimal cut-off point and discriminant ability (ROC curve). We assessed the salt intake using a food frequency questionnaire and a 24 h dietary recall and used a factor analysis to identify the foods with the highest contribution to be included in a high intake screening questionnaire. We used 24 h urinary sodium as a gold standard. We identified 38 foods and 14 factors representing a high intake, explaining a significant proportion of the total variance (50.3%). Significant correlations (r > 0.4) were obtained between nutritional survey scores and urinary sodium excretion, allowing us to detect patients who exceed salt intake recommendations. For sodium excretion ≥ 2.4 g/day, the survey has a sensitivity of 91.4%, a specificity of 96.2% and an area under the curve of 0.94. For a prevalence of high consumption of 57.4%, the positive predictive value (PPV) was 96.9% and the negative predictive value (NPV) was 89.2%. We developed a screening survey for subjects with a high probability of high salt intake in primary health care, which could contribute to the reduction in diseases associated with this consumption.

Predisposition to cortical neurodegenerative changes in brains of hypertension prone rats.

BACKGROUND: Substantial evidence suggests that hypertension is a significant risk factor for cognitive decline. However, it is unclear whether the genetic predisposition to hypertension is also associated with cellular dysfunction that promotes neurodegeneration. METHODS: Changes in blood pressure were evaluated following dietary salt-loading or administration of a regular diet in Sabra Normotensive (SBN/y) and Sabra Hypertension-prone rats (SBH/y). We performed quantitative RT-PCR and immunofluorescence staining in brain cortical tissues before salt loading and 6 and 9 months after salt loading. To examine the expression of brain cortical proteins involved in the gene regulation (Histone Deacetylase-HDAC2; Histone Acetyltransferase 1-HAT1), stress response (Activating Transcription Factor 4-ATF4; Eukaryotic Initiation Factor 2- eIF2α), autophagy (Autophagy related 4A cysteine peptidase- Atg4a; light-chain 3-LC3A/B; mammalian target of rapamycin complex 1- mTORC1) and apoptosis (caspase-3). RESULTS: Prior to salt loading, SBH/y compared to SBN/y expressed a significantly higher level of cortical HAT1 (protein), Caspase-3 (mRNA/protein), LC3A, and ATF4 (mRNA), lower levels of ATG4A (mRNA/protein), LC3A/B, HDAC2 (protein), as well as a lower density of cortical neurons. Following dietary salt loading, SBH/y but not SBN/y developed high blood pressure. In hypertensive SBH/y, there was significant upregulation of cortical HAT1 (protein), Caspase-3 (protein), and eIF2α ~ P (protein) and downregulation of HDAC2 (protein) and mTORC1 (mRNA), and cortical neuronal loss. CONCLUSIONS: The present findings suggest that genetic predisposition to hypertension is associated in the brain cortex with disruption in autophagy, gene regulation, an abnormal response to cellular stress, and a high level of cortical apoptosis, and could therefore exacerbate cellular dysfunction and thereby promote neurodegeneration.