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1.
Sodium Reduction: How Big Might the Risks and Benefits Be?
Yin, X, Tian, M, Neal, B
Heart, lung & circulation. 2021;(2):180-185
Abstract
Cardiovascular diseases are the leading cause of death worldwide and raised blood pressure is the leading risk for these conditions. Excess sodium intake clearly elevates blood pressure though the association of sodium intake with cardiovascular outcomes has been disputed. Nonetheless, it was estimated that in 2017 excess dietary sodium caused between 1.4 and 5.4 million deaths. Key underlying assumptions for those estimates were that the association between sodium intake and cardiovascular disease is direct and linear, and that a daily consumption level of 2.0 g of sodium minimised risk. Recent data indicating that reported U-shaped associations of sodium with risk are the result of confounding provide strong support for the first assumption. Cardiovascular risks may, however, continue to decline below intake levels of 2.0 g per day. Further, because excess sodium intake appears to drive a progressive rise in blood pressure with age, the magnitude of the disease burden avoidable by sodium reduction may have been under-estimated. Regardless, health benefits will only be achieved if safe, effective and scalable interventions can be defined and none have been identified to date. Salt substitution, which switches regular salt for a reduced-sodium, added-potassium alternative offers a significant opportunity. Falls in blood pressure with salt substitution are comparable to single-drug therapy and salt substitutes are low cost, simple to use, well-tolerated and could be applied community-wide. Data that prove clinical benefits and exclude risks will be required to support widespread use. An ongoing large-scale randomised trial of the effects of salt substitution on stroke, major cardiovascular events and death will complete soon and define the role of salt substitutes in public health.
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2.
The Feasibility of Using Computrition Software for Nutrition Research-A Pilot Study.
Millar, CL, Cohen, A, Juraschek, SP, Foley, A, Shtivelman, M, Mukamal, KJ, Sahni, S
Nutrients. 2021;(2)
Abstract
We evaluated the feasibility of using Computrition to design and implement a low vs. typical sodium meal plan intervention for older adults. Dietitians used Computrition to design a 7-day meal plan with three caloric levels (≤1750, 2000, ≥2250 kcals/day) and two sodium densities (low = 0.9 mg/kcal; n = 11 or typical = 2 mg/kcal; n = 9). Feasibility was determined by post-hoc definitions of effectiveness, sodium compliance, palatability of diet, sustainability, and safety. Given the low number of participants in one of the three calorie groups, the higher calorie groups were combined. Thus, comparisons are between low vs. typical meal plans at two calorie levels (≤1750 or ≥2000 kcals/day). Overall, regardless of the calorie group, the meal plans created with Computrition were effective in reaching the targeted sodium density and were safe for participants. Furthermore, individuals appeared to be equally compliant and reported similar palatability across meal plans. However, one of the three criteria for the sustainability definition was not met. In conclusion, we successfully used Computrition to design low and typical sodium meal plans that were effective, compliable, and safe. Future studies of older adults in similar settings should focus on improving the palatability of the meal plans and scaling this protocol to larger studies in older adults.
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3.
Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies.
Filippini, T, Malavolti, M, Whelton, PK, Naska, A, Orsini, N, Vinceti, M
Circulation. 2021;(16):1542-1567
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Abstract
BACKGROUND The relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose-response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose-response statistical models that can include 2-arm comparisons. METHODS After performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose-response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment. RESULTS We identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants' sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake. CONCLUSIONS In this dose-response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.
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Is There Association between Altered Adrenergic System Activity and Microvascular Endothelial Dysfunction Induced by a 7-Day High Salt Intake in Young Healthy Individuals.
Stupin, A, Drenjančević, I, Šušnjara, P, Debeljak, Ž, Kolobarić, N, Jukić, I, Mihaljević, Z, Martinović, G, Selthofer-Relatić, K
Nutrients. 2021;(5)
Abstract
This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines' level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals.
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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
Huang, L, Tian, M, Yu, J, Li, Q, Liu, Y, Yin, X, Wu, JH, Marklund, M, Wu, Y, Li, N, et al
American heart journal. 2020;:136-145
Abstract
The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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Impact of salt substitute and stepwise reduction of salt supply on blood pressure in residents in senior residential facilities: Design and rationale of the DECIDE-Salt trial.
Jin, A, Liu, K, Labarthe, DR, Feng, X, Zhang, R, Wang, H, Qiao, Q, Li, H, Li, J, Gao, P, et al
American heart journal. 2020;:198-205
Abstract
BACKGROUND High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed. METHODS The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death. CURRENT STATUS The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018. CONCLUSION The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.
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7.
Effect of salt reduction interventions in lowering blood pressure in Chinese populations: a systematic review and meta-analysis of randomised controlled trials.
Jin, A, Xie, W, Wu, Y
BMJ open. 2020;(2):e032941
Abstract
RATIONALE AND OBJECTIVE Salt reduction remains a global challenge and different salt reduction strategies have been studied in China. This study is to systematically evaluate evidence from randomised controlled trials (RCT) in China and inform the effective salt reduction strategies. DESIGN Systematic review and meta-analysis. DATA SOURCES MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Wanfang Data and the China National Knowledge Infrastructure databases through October 2019. ELIGIBILITY CRITERIA RCTs conducted in China with at least 4 weeks' duration of study and blood pressure (BP) reported. DATA EXTRACTION AND SYNTHESIS Data were screened, extracted and appraised by two independent reviewers. The quality of study was assessed using a modified Cochrane Collaboration's risk of bias tool. The primary outcome was the difference in BP change from baseline to the end of study between interventions and control. The effects were pooled using a random effects model and associated factors were explored by a meta-regression. RESULTS We identified 24 studies involving 10 448 participants, including 8 studies on health education (4583 participants), 2 studies on salt restriction diet (162 participants), 1 study on salt restriction spoon (50 participants) and 13 studies on salt substitute (5653 participants). Six studies on salt substitute and three studies on health education were identified with high quality. Pooled results from the six studies showed that salt substitutes significantly reduced systolic BP (-5.7 mm Hg; 95% CI -8.5 to -2.8) and diastolic BP (-2.0 mm Hg; 95% CI -3.5 to -0.4). The School-EduSalt study showed that the school-based health education significantly reduced systolic BP among parents (-2.3 mm Hg; 95% CI -4.5 to -0.04). CONCLUSIONS Among four salt reduction strategies studied in China with RCT design, only salt substitute was proved effective in lowering BP by the pooled effect from multiple studies with high quality. More well-designed studies are warranted for other strategies.
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8.
Priority Actions to Advance Population Sodium Reduction.
Ide, N, Ajenikoko, A, Steele, L, Cohn, J, J Curtis, C, Frieden, TR, Cobb, LK
Nutrients. 2020;(9)
Abstract
High sodium intake is estimated to cause approximately 3 million deaths per year worldwide. The estimated average sodium intake of 3.95 g/day far exceeds the recommended intake. Population sodium reduction should be a global priority, while simultaneously ensuring universal salt iodization. This article identifies high priority strategies that address major sources of sodium: added to packaged food, added to food consumed outside the home, and added in the home. To be included, strategies needed to be scalable and sustainable, have large benefit, and applicable to one of four measures of effectiveness: (1) Rigorously evaluated with demonstrated success in reducing sodium; (2) suggestive evidence from lower quality evaluations or modeling; (3) rigorous evaluations of similar interventions not specifically for sodium reduction; or (4) an innovative approach for sources of sodium that are not sufficiently addressed by an existing strategy. We identified seven priority interventions. Four target packaged food: front-of-pack labeling, packaged food reformulation targets, regulating food marketing to children, and taxes on high sodium foods. One targets food consumed outside the home: food procurement policies for public institutions. Two target sodium added at home: mass media campaigns and population uptake of low-sodium salt. In conclusion, governments have many tools to save lives by reducing population sodium intake.
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The Effects of Two Intervention Strategies to Reduce the Intake of Salt and the Sodium-To-Potassium Ratio on Cardiovascular Risk Factors. A 4-Month Randomised Controlled Study among Healthy Families.
Toft, U, Riis, NL, Lassen, AD, Trolle, E, Andreasen, AH, Frederiksen, AKS, Joergensen, NR, Munk, JK, Bjoernsbo, KS
Nutrients. 2020;(5)
Abstract
The aim was to examine the effects of two different salt reduction strategies on selected cardiovascular risk factors. The study was a four-month cluster randomised controlled study. Eighty-nine healthy Danish families (309 individuals) were randomly assigned to either (A) gradually salt-reduced bread, (B) gradually salt-reduced bread and dietary counselling to further reduce salt intake and increase potassium intake or (C) standard bread (control). The effect was assessed using linear mixed models. Intention to treat analyses comparing changes in the three groups showed a significant reduction in body fat percent (-1.31% (-2.40; -0.23)) and a borderline significant reduction in total plasma cholesterol (-0.25 mmol/L (-0.51; 0.01) and plasma renin (-0.19 pmol/L (-0.39; 0.00) in group A compared to the control group. Adjusted complete case analyses showed a significant reduction in total plasma cholesterol (-0.29 mmol/L (-0.50; -0.08), plasma LDL cholesterol (-0.08 mmol/L (-0.15; -0.00)), plasma renin (-0.23 pmol/L (-0.41; -0.05)), plasma adrenaline (-0.03 nmol/L (-0.06; -0.01)) and body fat percent (-1.53% (-2.51; -0.54)) in group A compared to the control group. No significant changes were found in group B compared to the control group. In conclusion, receiving sodium reduce bread was associated with beneficial changes in cardiovascular risk factors. No adverse effects were observed.
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10.
Potassium-Enriched Salt Substitutes as a Means to Lower Blood Pressure: Benefits and Risks.
Greer, RC, Marklund, M, Anderson, CAM, Cobb, LK, Dalcin, AT, Henry, M, Appel, LJ
Hypertension (Dallas, Tex. : 1979). 2020;(2):266-274
Abstract
Use of salt substitutes containing potassium chloride is a potential strategy to reduce sodium intake, increase potassium intake, and thereby lower blood pressure and prevent the adverse consequences of high blood pressure. In this review, we describe the rationale for using potassium-enriched salt substitutes, summarize current evidence on the benefits and risks of potassium-enriched salt substitutes and discuss the implications of using potassium-enriched salt substitutes as a strategy to lower blood pressure. A benefit of salt substitutes that contain potassium chloride is the expected reduction in dietary sodium intake at the population level because of reformulation of manufactured foods or replacement of sodium chloride added to food during home cooking or at the dining table. There is empirical evidence that replacement of sodium chloride with potassium-enriched salt substitutes lowers systolic and diastolic blood pressure (average net Δ [95% CI] in mm Hg: -5.58 [-7.08 to -4.09] and -2.88 [-3.93 to -1.83], respectively). The risks of potassium-enriched salt substitutes include a possible increased risk of hyperkalemia and its principal adverse consequences: arrhythmias and sudden cardiac death, especially in people with conditions that impair potassium excretion such as chronic kidney disease. There is insufficient evidence regarding the effects of potassium-enriched salt substitutes on the occurrence of hyperkalemia. There is a need for additional empirical research on the effect of increasing dietary potassium and potassium-enriched salt substitutes on serum potassium levels and the risk of hyperkalemia, as well as for robust estimation of the population-wide impact of replacing sodium chloride with potassium-enriched salt substitutes.