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Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in Humans.
Basdeki, ED, Kollias, A, Mitrou, P, Tsirimiagkou, C, Georgakis, MK, Chatzigeorgiou, A, Argyris, A, Karatzi, K, Manios, Y, Sfikakis, PP, et al
Nutrients. 2021;(8)
Abstract
Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(-0.3, 0.4) mg/L; TNF-a -0.7(-5.0, 3.6) pg/mL; IL-6 -1.1(-3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, "normal" and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.
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Effect of dietary sodium restriction on blood pressure in type 2 diabetes: A meta-analysis of randomized controlled trials.
Ren, J, Qin, L, Li, X, Zhao, R, Wu, Z, Ma, Y
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(6):1653-1661
Abstract
AIMS: Although current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) of sodium restriction and blood pressure (BP) in patients with T2DM. DATA SYNTHESIS We performed a systematic search of the online databases that evaluated the effect of dietary sodium restriction on BP in patients with T2DM. Sodium intake was expressed by 24 h urinary sodium excretion (UNaV). Q statistics and I2 were used to explore between-study heterogeneity. A random-effects model was used in the presence of significant heterogeneity; otherwise, a fixed-effects model was applied. Eight RCTs with 10 trials (7 cross-over and 3 parallel designs) were included in the meta-analysis. Compared with ordinary sodium intake, dietary sodium restriction significantly decreased UNaV (weighted mean difference, WMD: -38.430 mmol/24 h; 95% CI: -41.665 mmol/24 h to -35.194 mmol/24 h). Sodium restriction significantly lowered systolic BP (WMD: -5.574 mm Hg; 95% CI: -8.314 to -2.834 mm Hg; I2 = 0.0%) and diastolic BP (WMD: -1.675 mm Hg; 95% CI: -3.199 to -0.150 mm Hg; I2 = 0.0%) with low heterogeneity among the studies. No publication bias was found from Begg's and Egger's tests. CONCLUSIONS Sodium restriction significantly reduces SBP and DBP in patients with T2DM.
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Sodium and Salt Consumption in Latin America and the Caribbean: A Systematic-Review and Meta-Analysis of Population-Based Studies and Surveys.
Carrillo-Larco, RM, Bernabe-Ortiz, A
Nutrients. 2020;(2)
Abstract
Sodium/salt consumption is a risk factor for cardiovascular diseases. Although global targets to reduce salt intake have been established, current levels and trends of sodium consumption in Latin America and the Caribbean (LAC) are unknown. We conducted a systematic review and meta-analysis of population-based studies in which sodium consumption was analyzed based on urine samples (24 hour samples or otherwise). The search was conducted in Medline, Embase, Global Health, Scopus and LILACS. From 2350 results, 53 were studied in detail, of which 15 reports were included, providing evidence for 18 studies. Most studies were from Brazil (7/18) and six collected 24 hour urine samples. In the random effects meta-analysis, 12 studies (29,875 people) were analyzed since 2010. The pooled mean 24 hour estimated sodium consumption was 4.13 g/day (10.49 g/day of salt). When only national surveys were analyzed, the pooled mean was 3.43 g/day (8.71 g/day of salt); when only community studies were analyzed the pooled mean was 4.39 g/day (11.15 g/day of salt). Studies had low risk of bias. The estimated 24 hour sodium consumption is more than twice the World Health Organization recommendations since 2010. Regional organizations and governments should strengthen policies and interventions to measure and reduce sodium consumption in LAC.
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Genome-Wide Association Meta-Analysis of Individuals of European Ancestry Identifies Suggestive Loci for Sodium Intake, Potassium Intake, and Their Ratio Measured from 24-Hour or Half-Day Urine Samples.
Kho, M, Smith, JA, Verweij, N, Shang, L, Ryan, KA, Zhao, W, Ware, EB, Gansevoort, RT, Irvin, MR, Lee, JE, et al
The Journal of nutrition. 2020;(10):2635-2645
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Abstract
BACKGROUND Excess sodium intake and insufficient potassium intake are risk factors for hypertension, but there is limited knowledge regarding genetic factors that influence intake. Twenty-hour or half-day urine samples provide robust estimates of sodium and potassium intake, outperforming other measures such as spot urine samples and dietary self-reporting. OBJECTIVE The aim of this study was to investigate genomic regions associated with sodium intake, potassium intake, and sodium-to-potassium ratio measured from 24-h or half-day urine samples. METHODS Using samples of European ancestry (mean age: 54.2 y; 52.3% women), we conducted a meta-analysis of genome-wide association studies in 4 cohorts with 24-h or half-day urine samples (n = 6,519), followed by gene-based analysis. Suggestive loci (P < 10-6) were examined in additional European (n = 844), African (n = 1,246), and Asian (n = 2,475) ancestry samples. RESULTS We found suggestive loci (P < 10-6) for all 3 traits, including 7 for 24-h sodium excretion, 4 for 24-h potassium excretion, and 4 for sodium-to-potassium ratio. The most significant locus was rs77958157 near cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) , a gene involved in eating behavior and appetite regulation (P = 2.3 × 10-8 with sodium-to-potassium ratio). Two suggestive loci were replicated in additional samples: for sodium excretion, rs12094702 near zinc finger SWIM-type containing 5 (ZSWIM5) was replicated in the Asian ancestry sample reaching Bonferroni-corrected significance (P = 0.007), and for potassium excretion rs34473523 near sodium leak channel (NALCN) was associated at a nominal P value with potassium excretion both in European (P = 0.043) and African (P = 0.043) ancestry cohorts. Gene-based tests identified 1 significant gene for sodium excretion, CDC42 small effector 1 (CDC42SE1), which is associated with blood pressure regulation. CONCLUSIONS We identified multiple suggestive loci for sodium and potassium intake near genes associated with eating behavior, nervous system development and function, and blood pressure regulation in individuals of European ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake.
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Comparison of 24-hour urine and 24-hour diet recall for estimating dietary sodium intake in populations: A systematic review and meta-analysis.
McLean, R, Cameron, C, Butcher, E, Cook, NR, Woodward, M, Campbell, NRC
Journal of clinical hypertension (Greenwich, Conn.). 2019;(12):1753-1762
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Abstract
This systematic literature review and meta-analysis examined whether 24-hour diet recall is a valid way to measure mean population sodium intake compared with the gold standard 24-hour urinary assessment. The authors searched electronic databases MEDLINE, Embase, and Scopus using pre-defined terms. Studies were eligible for inclusion if they assessed adult humans in free-living settings, and if they included group means for 24-hour diet recall and 24-hour urinary collection of sodium intake in the same participants. Studies that included populations with an active disease state that might interfere with normal sodium metabolism were excluded. Results of 28 studies are included in the meta-analysis. Overall, 24-hour diet recall underestimated population mean sodium intake by an average of 607 mg per day compared to the 24-hour urine collection. The difference between measures from 24-hour urine and 24-hour diet recall was smaller in studies conducted in high-income countries, in studies where multiple-pass methods of 24-hour diet recall were reported and where urine was validated for completeness. Higher quality studies also reported smaller differences between measures than lower quality studies. Monitoring of population sodium intake with 24-hour urinary excretion remains the most accurate method of assessment. Twenty-four-hour diet recall tends to underestimate intake, although high-quality 24-hour diet recall improves accuracy, and may be used if 24-hour urine is not feasible.
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Sodium status and the metabolic syndrome: A systematic review and meta-analysis of observational studies.
Soltani, S, Kolahdouz Mohammadi, R, Shab-Bidar, S, Vafa, M, Salehi-Abargouei, A
Critical reviews in food science and nutrition. 2019;(2):196-206
Abstract
The prevalence of metabolic syndrome (MetS) has been greatly increased, worldwide. In recent years, investigators have proposed that sodium might contribute to the development of metabolic syndrome; however, the published data were conflicting. The present systematic review aimed to summarize the evidence from observational studies in this regard. We conducted a systematic search for relevant observational studies investigating the association between sodium status and MetS, published until June 2017 in electronic databases including PubMed, EMBASE, Scopus and Google Scholar. Summary effects were derived using random effects model. After screening the records, seventeen publications with 66,274 participants were eligible to be included in the systematic review and meta-analysis. The analysis revealed that subjects with MetS have significantly higher levels of sodium compared to healthy controls (Hedges' g = 0.21, 95% CI: 0.12, 0.29, I2 = 68.6). Subgroup analyses revealed that the difference was significant when the sodium status was assessed using urinary sodium levels. The random effects meta-regression analysis also revealed that body sodium level increases with the number of MetS components. Furthermore, participants with highest dietary/urinary or serum sodium levels had 37% higher chance of developing MetS when compared with participants with the lowest sodium levels (OR = 1.37 95%CI: 1.31, 1.42, I2 = 86.9). The current meta-analysis revealed that higher sodium input into the body is directly associated with the likelihood of MetS. Prospective cohort studies and well-designed randomized clinical trials considering the effect of sodium restricted diets on the risk of MetS as an outcome are necessary to represent the causal association.
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Dose-response association of dietary sodium intake with all-cause and cardiovascular mortality: a systematic review and meta-analysis of prospective studies.
Milajerdi, A, Djafarian, K, Shab-Bidar, S
Public health nutrition. 2019;(2):295-306
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OBJECTIVE High Na intake has been associated with different health problems. However, serious controversies exist over studies investigating associations of Na intake with mortality from all-causes and CVD. The present systematic review and meta-analysis was done to investigate, for the first time, the dose-response association of dietary Na intake with all-cause and CVD mortality among prospective studies. DESIGN Relevant papers published up to August 2017 were searched in MEDLINE, EMBASE and Google Scholar databases. Prospective cohort studies on the association of dietary Na intake with all-cause or/and CVD mortality were included. Linear and non-linear dose-response associations between Na intake and CVD and all-cause mortality were examined. RESULTS Overall, twenty publications met inclusion criteria. A significant non-linear association (P<0·001) was found between Na intake and CVD mortality risk among studies assessing urinary Na excretion, with a relatively steep slope at Na intakes above 2400mg/d. However, the association was not significant in studies using dietary Na intake (P=0·61). Additionally, the non-linear association of Na intake with all-cause mortality was also non-significant. No linear association (effect size; 95 % CI; I 2) was seen between 100mg/d increment in Na intake and CVD mortality (1·01; 0·97, 1·05; 98·4 %) or all-cause mortality (1·01; 1·00, 1·02; 89·2 %). Following subgroup analyses, the association between Na intake and CVD mortality was observed only among studies conducted in the USA (0·99; 0·99, 1·00; 20·0 %). CONCLUSIONS The study showed a direct association between urinary Na excretion and CVD mortality which was more considerable at intakes above 2400mg/d. In contrast, no significant association was found between Na intake and all-cause mortality. Further long-term prospective studies on different populations are required to confirm these findings.
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Association of sodium intake and major cardiovascular outcomes: a dose-response meta-analysis of prospective cohort studies.
Zhu, Y, Zhang, J, Li, Z, Liu, Y, Fan, X, Zhang, Y, Zhang, Y
BMC cardiovascular disorders. 2018;(1):192
Abstract
BACKGROUND The association of sodium intake with the risk of cardiovascular morbidity and mortality is inconsistent. Thus, the present meta-analysis was conducted to summarize the strength of association between sodium intake and cardiovascular morbidity and mortality. METHODS PubMed, Embase, and the Cochrane Library were searched systematically to identify the relevant studies up to October 2017. The effect estimates for 100 mmol/day increase in sodium intake were calculated using 95% confidence intervals (CIs) of cardiac death, total mortality, stroke, or stroke mortality for low (< 3 g/d), moderate (3-5 g/d), or heavy (> 5 g/d) sodium intake, and minimal sodium intake comparison. RESULTS A total of 16 prospective cohort studies reported data on 205,575 individuals. The results suggested that an increase in sodium intake by 100 mmol/d demonstrated little or no effect on the risk of cardiac death (P = 0.718) and total mortality (P = 0.720). However, the risk of stroke incidence (P = 0.029) and stroke mortality (P = 0.007) was increased significantly by 100 mmol/day increment of sodium intake. Furthermore, low sodium intake was associated with an increased risk of cardiac death (P = 0.003), while moderate (P < 0.001) or heavy (P = 0.001) sodium intake was associated with an increased risk of stroke mortality. CONCLUSIONS These findings suggested that sodium intake by 100 mmol/d increment was associated with an increased risk of stroke incidence and stroke mortality. Furthermore, low sodium intake was related to an increased cardiac death risk, while moderate or heavy sodium intake was related to an increased risk of stroke mortality.
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Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies.
Mente, A, O'Donnell, M, Rangarajan, S, Dagenais, G, Lear, S, McQueen, M, Diaz, R, Avezum, A, Lopez-Jaramillo, P, Lanas, F, et al
Lancet (London, England). 2016;(10043):465-75
Abstract
BACKGROUND Several studies reported a U-shaped association between urinary sodium excretion and cardiovascular disease events and mortality. Whether these associations vary between those individuals with and without hypertension is uncertain. We aimed to explore whether the association between sodium intake and cardiovascular disease events and all-cause mortality is modified by hypertension status. METHODS In this pooled analysis, we studied 133,118 individuals (63,559 with hypertension and 69,559 without hypertension), median age of 55 years (IQR 45-63), from 49 countries in four large prospective studies and estimated 24-h urinary sodium excretion (as group-level measure of intake). We related this to the composite outcome of death and major cardiovascular disease events over a median of 4.2 years (IQR 3.0-5.0) and blood pressure. FINDINGS Increased sodium intake was associated with greater increases in systolic blood pressure in individuals with hypertension (2.08 mm Hg change per g sodium increase) compared with individuals without hypertension (1.22 mm Hg change per g; pinteraction<0.0001). In those individuals with hypertension (6835 events), sodium excretion of 7 g/day or more (7060 [11%] of population with hypertension: hazard ratio [HR] 1.23 [95% CI 1.11-1.37]; p<0.0001) and less than 3 g/day (7006 [11%] of population with hypertension: 1.34 [1.23-1.47]; p<0.0001) were both associated with increased risk compared with sodium excretion of 4-5 g/day (reference 25% of the population with hypertension). In those individuals without hypertension (3021 events), compared with 4-5 g/day (18,508 [27%] of the population without hypertension), higher sodium excretion was not associated with risk of the primary composite outcome (≥ 7 g/day in 6271 [9%] of the population without hypertension; HR 0.90 [95% CI 0.76-1.08]; p=0.2547), whereas an excretion of less than 3 g/day was associated with a significantly increased risk (7547 [11%] of the population without hypertension; HR 1.26 [95% CI 1.10-1.45]; p=0.0009). INTERPRETATION Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets. FUNDING Full funding sources listed at end of paper (see Acknowledgments).
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Dietary sodium intake and overweight and obesity in children and adults: a protocol for a systematic review and meta-analysis.
Grimes, CA, Bolhuis, DP, He, FJ, Nowson, CA
Systematic reviews. 2016;:7
Abstract
BACKGROUND Overweight and obesity in children and adults is a major public health concern. Emerging evidence suggests dietary sodium intake may be associated with obesity. This systematic review and meta-analysis will aim to (i) assess the relation between dietary sodium intake and measures of adiposity in children and adults and (ii) examine the relation between sodium intake and sugar-sweetened beverage (SSB) consumption, which is a known risk factor for obesity. METHODS/DESIGN An electronic search will be conducted using Medline Complete, CINAHL, Scopus, Embase and Cochrane central register of controlled trials (CENTRAL). The search strategy will identify published peer-reviewed articles that report on dietary sodium and either a marker of adiposity or SSB consumption. Only human studies (ages >1 year) in English will be included, and no limits will be placed on publication date. No restrictions will be placed on the method of sodium intake assessment. Cross-sectional, prospective studies, and randomised controlled trials with a duration of ≥ 3 months will be included. Studies with participants with renal disease, cancer, type 1 diabetes or heart failure or who are pregnant will be excluded. To assess the quality of studies, the Cochrane's Collaboration tool for assessing risk of bias in randomised trials will be used for randomised controlled trials (RCTs), and the modified Newcastle-Ottawa Scale will be used for cross-sectional and prospective studies. Meta-analysis will be used to assess the relation of sodium intake with two primary outcomes: (i) BMI and body weight in adults and BMI z-score in children and (ii) weight category (i.e. healthy weight vs. overweight/obese). For any outcomes in which meta-analysis is not possible, we will present data as a systematic review. Findings will be grouped and reported separately for children and adolescents (ages 1-17 years) and adults (ages >18 years). DISCUSSION This review and meta-analysis will provide insight into the relation between dietary sodium intake and overweight and obesity. This information can be used to inform public health policies which target population sodium consumption. SYSTEMATIC REVIEW REGISTRATION Prospero CRD42015016440.